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1.
Louise Emmett Megan Crumbaker Bao Ho Kathy Willowson Peter Eu Lalith Ratnayake Richard Epstein Ashley Blanksby Lisa Horvath Alex Guminski Kate Mahon Craig Gedye Charlotte Yin Phillip Stricker Anthony M. Joshua 《Clinical genitourinary cancer》2019,17(1):15-22
Background
177Lu–PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial.Patients and Methods
Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no 18F-Fluoro–deoxyglucose (FDG) PET-discordant disease. Men received up to 4 cycles of Lu-PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate-specific antigen (PSA) progression. The study assessed treatment response to Lu-PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment.Results
Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression.Conclusion
PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options. 相似文献2.
Background
Although standard-dose total skin electron beam therapy (TSEBT) has been thought to provide the greatest clinical benefit for mycosis fungoides, recent studies have shown that low-dose TSEBT may also provide high rates of disease control.Materials and Methods
A retrospective chart review was conducted for patients receiving TSEBT for mycosis fungoides at a single institution from 2009 to 2017. Patients were evaluated for overall survival, progression-free survival, and duration of clinical benefit. Partial response was defined as any documented clinical regression of lesions, whereas complete response was defined as complete resolution of lesions.Results
Twenty patients were included in the study. Twelve patients received low-dose radiation (≤ 12 Gy), and 8 received standard-dose radiation (> 12 Gy). Response rate was 100% in both groups. The rate of complete response was 38% in the standard-dose group and 25% in the low-dose group. There was no difference in overall survival between the 2 groups (P = .84). There was also no difference in median progression-free survival (P = .95) or duration of clinical benefit (P = .95) between the 2 groups. Of low-dose patients, 33% received immediate systemic therapy, whereas 92% received adjuvant topical or systemic therapy. In the standard-dose group, only 25% received systemic adjuvant therapy, and 63% received adjuvant topical or systemic therapy.Conclusion
Low-dose TSEBT with adjuvant therapy results in adequate symptom palliation, comparable to standard-dose TSEBT. Low-dose TSEBT should be considered a standard treatment option in this population. 相似文献3.
Background
Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study.Patients and Methods
We performed a retrospective analysis of the prospectively collected data among patients with metastatic HSPC in the CHAARTED study, a phase 3 multicenter study conducted between 2006 and 2014. The CHAARTED study compared androgen deprivation therapy plus docetaxel versus androgen deprivation therapy alone among patients with metastatic HSPC. The main outcomes of the current analysis are overall survival, progression-free survival, prostate cancer–specific survival, and time to castration-resistant disease as assessed by Kaplan-Meier analysis, log-rank testing, and Cox regression models.Results
Kaplan-Meier overall survival estimates were produced according to whether patients underwent prior local treatment and results were stratified by treatment arm. For both treatment arms, patients with prior local treatment had better overall survival (P < .01). Similarly, Kaplan-Meier progression-free survival estimates were produced according to whether patients underwent prior local treatment, and results were stratified by the treatment arm. For both treatment arms, patients with prior local treatment had better progression-free survival (P < .01). In an adjusted Cox multivariate model (adjusted for assigned study treatment arm, age, baseline prostate-specific antigen, and baseline Gleason score, volume of the disease (low risk or high risk) and baseline performance status), patients with prior local treatment had better overall survival (P = .045), progression-free survival (P = .035), and cancer-specific survival (P = .010) compared to those without prior local treatment. Moreover, they had a longer time to development of castration-resistant disease (P = .025).Conclusion
Patients with metastatic HSPC and prior local treatment had better overall, progression-free, and cancer-specific survivals compared to those without prior local treatment. The impact of these findings on the treatment paradigms for metastatic HSPC should be thoroughly evaluated. 相似文献4.
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5.
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6.
J. Connor Wells Dongsheng Tu Lillian L. Siu Jeremy D. Shapiro Derek J. Jonker Christos Karapetis John Simes Geoffrey Liu Timothy J. Price Niall C. Tebbutt Chris J. O’Callaghan 《Clinical colorectal cancer》2019,18(1):e140-e149
Background
The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated.Patients and Methods
Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. best supportive care) and CO.20 (cetuximab plus placebo vs. cetuximab plus brivanib). Only patients with wild-type KRAS tumors were included.Results
A total of 251 (26.3%) of 955 patients were ≥ 70 years old. No significant differences in OS, PFS, or grade 3/4 adverse events were observed between older and younger patients treated with cetuximab (or cetuximab with placebo) in either trial. Younger patients trended toward superior OS in both CO.17 (hazard ratio = 1.80; P = .16) and CO.20 (hazard ratio = 1.34; P = .07). QoL maintenance favored younger patients in CO.17 (3.6 vs. 5.7 months; P = .046) but no difference of QoL maintenance was observed in the larger CO.20 trial (1.7 vs. 1.8 months; P = .64). Combination therapy of cetuximab and brivanib was significantly more toxic in older adults (87% vs. 77%; P = .03).Conclusion
OS, PFS, and toxicities were similar between older and younger patients with wild-type KRAS metastatic colorectal cancer when treated with cetuximab. Both age groups likely experience similar QoL maintenance with cetuximab. Dual targeted therapy was significantly more toxic in older patients. 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.
Yasir Y. Elamin Daniel R. Gomez Mara B. Antonoff Jacqulyne P. Robichaux Hai Tran Melissa K. Shorter Jadi M. Bohac Marcelo Vailati Negrao Xiuning Le Waree Rinsurogkawong Jeff Lewis Lara Lacerda Emily B. Roarty Stephen G. Swisher Jack A. Roth Jianjun Zhang Vassiliki Papadimitrakopoulou John V. Heymach 《Clinical lung cancer》2019,20(1):43-47
Introduction
Although most NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutations have an impressive initial response, the vast majority has residual disease and develops acquired resistance after 9 to 14 months of EGFR tyrosine kinase (TKI) therapy. We recently reported a phase II trial showing that, for patients with molecularly unselected oligometastatic NSCLC who did not progress after first-line systemic therapy, local consolidation therapy (LCT) with surgery or radiation improved progression-free survival (PFS), compared with maintenance therapy alone. Herein, we report a retrospective analysis of LCT after TKI in patients with metastatic EGFR mutant NSCLC.Patients and Methods
We identified patients with metastatic EGFR mutant NSCLC treated with TKI plus LCT or with TKI alone in the MD Anderson GEMINI (Genomic Marker-Guided Therapy Initiative) database and in our recently published LCT trial. PFS was compared between LCT plus TKI and TKI only treated patients using the log-rank test.Results
We identified 129 patients with EGFR mutant NSCLC who were treated with first-line TKI and 12 that were treated with TKI followed by LCT. Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤ 3 metastases), and 4 patients had > 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for 1 patient. TKI followed by LCT resulted in a significantly longer PFS (36 months) compared with TKI alone (PFS, 14 months; log-rank P = .0024).Conclusions
Our data suggests that first-line TKI plus LCT is a promising therapeutic strategy for patients with EGFR mutant NSCLC that merits further investigation. 相似文献9.
Cristina Masini Maria Giuseppa Vitale Marco Maruzzo Giuseppe Procopio Ugo de Giorgi Sebastiano Buti Sabrina Rossetti Roberto Iacovelli Francesco Atzori Laura Cosmai Francesca Vignani Giuseppe Prati Sarah Scagliarini Annalisa Guida Annalisa Berselli Carmine Pinto 《Clinical genitourinary cancer》2019,17(1):e150-e155
Background
Pazopanib has been approved for first-line treatment of patients with metastatic renal-cell carcinoma on the basis of clinical trials that enrolled only patients with adequate renal function. Few data are available on the safety and efficacy of pazopanib in patients with renal insufficiency. This study investigated the effect of kidney function on treatment outcomes in such patients.Patients and Methods
We retrospectively analyzed data of metastatic renal-cell carcinoma patients treated with pazopanib from January 2010 to June 2016 with respect to renal function. Patients with Modification of Diet in Renal Disease ≤ 60 mL/min/1.73 m2 (group A) were compared to patients with Modification of Diet in Renal Disease > 60 mL/min/1.73 m2 (group B) in terms of progression-free survival, toxicities, response rates, and overall survival.Results
A total of 229 patients were included: 128 in group A and 101 in group B. Median progression-free survival was 14 months (95% confidence interval [CI], 9.4-18.5) and 17 months (95% CI, 11.4-22.8), and overall survival was 30.5 months (95% CI, 8-53) and 41.4 months (95% CI, 21-62) for group A and group B, respectively, with no significant difference (P = .6). No significant difference between the 2 groups was reported in the incidence of adverse events. Dose reductions were more frequent in group A patients (66% vs. 36%; P = .04).Conclusion
Although the dose of pazopanib was reduced more frequently in patients with renal impairment, kidney function at therapy initiation does not adversely affect the safety and efficacy of pazopanib. 相似文献10.
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11.
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12.
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13.
Fang Hu Jianlin Xu Bo Zhang Changhui Li Wei Nie Ping Gu Ping Hu Huimin Wang Yujun Zhang Yinchen Shen Shuyuan Wang Xueyan Zhang 《Clinical lung cancer》2019,20(1):e81-e90
Background
For oligometastatic lung adenocarcinoma patients with sensitive epidermal growth factor receptor (EGFR) mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in oligometastatic lung adenocarcinoma patients.Patients and Methods
We conducted a retrospective study to assess the effects of LCT on progression-free survival (PFS) and overall survival (OS). Patients with advanced-stage oligometastatic lung adenocarcinoma harboring sensitive mutation of epidermal growth factor receptor (EGFR) who received EGFR–tyrosine kinase inhibitor (TKI) or EGFR-TKI plus LCT were admitted to Shanghai Chest Hospital from January 2010 to December 2016. The PFS and OS of the 2 groups were accordingly analyzed.Results
A total of 231 patients (143 patients who received LCT plus EGFR-TKI [combination group] and 88 patients who only received EGFR-TKI only [monotherapy group]) were included in this study. Median PFS was significantly longer in the combination group (15 months; 95% confidence interval [CI], 13.611-16.389) than in the monotherapy group (10 months; 95% CI, 8.936-11.064; hazard ratio = 0.610; 95% CI, 0.461, 0.807; P = .000). The median OS in the combination group was 34 months (95% CI, 27.889, 40.111) versus 21 months (95% CI, 18.445, 23.555) in the monotherapy group (hazard ratio = 0.593; 95% CI, 0.430-0.817; P = .001).Conclusion
LCT combined with TKIs therapy was a feasible method that significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with EGFR mutations, and it thus might be considered as an important medical treatment during clinical management. 相似文献14.
S. Roy M. Sia S. Tyldesley G. Bahl 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):91-98
Aims
To evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database.Patients and methods
Patients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005–2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005–2007 and 139/2542 from 2010–2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan–Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010–2014).Results
The median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5–108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7–11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32–10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58–9.46, P = 0.003).Conclusion
This study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca. 相似文献15.
Andrew W. Hahn David M. Gill Roberto H. Nussenzveig Austin Poole Jim Farnham Lisa Cannon-Albright Neeraj Agarwal 《Clinical genitourinary cancer》2018,16(4):288-292
Background
The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, the HSD3B1 (1245C) variant was shown to predict shorter duration of response to androgen deprivation therapy with medical or surgical castration in the setting of castration-sensitive prostate cancer (CSPC). The HSD3B1 (1245C) variant also predicts longer duration of response to ketoconazole in men with castration-resistant prostate cancer (CRPC). We hypothesized that the HSD3B1 (1245C) variant predicts response to treatment with abiraterone acetate (AA) and can help personalize treatment in men with advanced prostate cancer.Methods
Clinical data and samples were from a prospectively maintained prostate cancer registry at the University of Utah. Genotyping was performed. The primary study end point was progression-free survival in first-line AA in men with metastatic CRPC. We performed prespecified multivariate analyses to assess the independent predictive value of HSD3B1 genotype on progression-free survival on AA.Results
Seventy-six men with metastatic CRPC treated with first-line AA were included. In multivariate analysis, the HSD3B1 (1245C) variant did not predict response to first-line AA.Conclusion
The HSD3B1 (1245C) variant does not predict response to first-line AA in metastatic CRPC. This finding could be due to the ability of AA metabolites to act as both agonist (3-keto-5α-abiraterone) and antagonist (Δ4-abiraterone) on androgen signaling. 相似文献16.
Martin Reck Leora Horn Silvia Novello Fabrice Barlesi István Albert Erzsébet Juhász Dariusz Kowalski Gilles Robinet Jacques Cadranel Paolo Bidoli John Chung Arno Fritsch Uta Drews Andrea Wagner Ramaswamy Govindan 《Journal of thoracic oncology》2019,14(4):701-711
Introduction
This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.Methods
In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days–on, 4 days–off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.Results
A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2–5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6–5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820–1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9–11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7–11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776–1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).Conclusions
Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated. 相似文献17.
Hossein Borghaei Corey J. Langer Shirish Gadgeel Vassiliki A. Papadimitrakopoulou Amita Patnaik Steven F. Powell Ryan D. Gentzler Renato G. Martins James P. Stevenson Shadia I. Jalal Amit Panwalkar James Chih-Hsin Yang Matthew Gubens Lecia V. Sequist Mark M. Awad Joseph Fiore Sanatan Saraf Steven M. Keller Leena Gandhi 《Journal of thoracic oncology》2019,14(1):124-129
Introduction
Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42?1.91). Herein, we present an updated analysis.Methods
A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025).Results
As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%?42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33?0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti?programmed death 1/anti?programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32?0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events.Conclusions
The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC. 相似文献18.
Vanesa Ortega Antonio Antón Isabel Garau Noemia Afonso Lourdes Calvo Yolanda Fernández María Martínez-García Esperanza Blanco Pilar Zamora Mirta García José Juan Illarramendi César Augusto Rodríguez Sánchez Miguel Sampayo Elena Aguirre José Manuel Pérez-García Javier Cortés Antonio Llombart-Cussac 《Clinical breast cancer》2019,19(2):105-112
Background
Eribulin has efficacy in patients with progression after ≥ 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors.Patients and Methods
Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received ≥ 1 dose of eribulin.Results
The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia.Conclusion
Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC. 相似文献19.
C.M. Jones K. Spencer C. Hitchen T. Pelly B. Wood P. Hatfield A. Crellin D. Sebag-Montefiore R. Goody T. Crosby G. Radhakrishna 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(6):356-364
Aims
Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen.Materials and methods
A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50–52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre.Results
Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48–1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25–0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23–0.88) when compared with HRT.Conclusions
The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated. 相似文献20.
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