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1.
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2.
Sara Gagno Mario Rosario D’Andrea Mauro Mansutti Chiara Zanusso Fabio Puglisi Eva Dreussi Marcella Montico Paola Biason Erika Cecchin Donatella Iacono Stefania Russo Marika Cinausero Silvana Saracchini Giampietro Gasparini Donata Sartori Mario Bari Elena Collovà Rosa Meo Giuseppe Toffoli 《Clinical breast cancer》2019,19(2):137-145.e4
Introduction
Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival.Patients and Methods
Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility.Results
Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor–4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively.Conclusion
In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management. 相似文献3.
Khurum Khan Jayant K. Rane David Cunningham Sheela Rao David Watkins Naureen Starling Eleftheria Kalaitzaki Martin Forster Chiara Braconi Nicola Valeri Marco Gerlinger Ian Chau 《Clinical colorectal cancer》2019,18(1):64-71.e1
Background
Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy.Patients and Methods
Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis.Results
A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively.Conclusion
A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors. 相似文献4.
Yi-Long Wu Shun Lu Ying Cheng Caicun Zhou Jie Wang Tony Mok Li Zhang Hai-Yan Tu Lin Wu Jifeng Feng Yiping Zhang Alexander Valerievich Luft Jianying Zhou Zhiyong Ma You Lu Chengping Hu Yuankai Shi Christine Baudelet Jianhua Chang 《Journal of thoracic oncology》2019,14(5):867-875
Introduction
Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated NSCLC.Methods
CheckMate 078 was a randomized, open-label, phase III clinical trial in patients from China, Russia, and Singapore with squamous or nonsquamous NSCLC that had progressed during/after platinum-based doublet chemotherapy (ClinicalTrials.gov: NCT02613507). Patients with EGFR/ALK alterations were excluded. Patients (N = 504) were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, tumor histology, and tumor programmed death ligand 1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate, progression-free survival, and safety.Results
OS was significantly improved with nivolumab (n = 338) versus docetaxel (n = 166); median OS (95% confidence interval): 12.0 (10.4–14.0) versus 9.6 (7.6–11.2) months, respectively; hazard ratio (97.7% confidence interval): 0.68 (0.52–0.90); p = 0.0006. Objective response rate was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5.3 months. Minimum follow-up was 8.8 months. The frequency of grade 3 or greater treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.Conclusions
This is the first phase III study in a predominantly Chinese population reporting results with a programmed death 1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies. 相似文献5.
6.
Maxime Vanmechelen Diether Lambrechts Thomas Van Brussel Annelies Verbiest Gabrielle Couchy Patrick Schöffski Herlinde Dumez Philip R. Debruyne Evelyne Lerut Jean-Pascal Machiels Vincent Richard Maarten Albersen Vincent Verschaeve Stéphane Oudard Arnaud Méjean Pascal Wolter Jessica Zucman-Rossi Benoit Beuselinck 《Clinical genitourinary cancer》2019,17(2):e235-e246
Background
There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib.Materials and Methods
Germline DNA was collected in patients with mccRCC starting first-line systemic therapy with sunitinib. SNP rs2981582 in FGFR2 C>T was genotyped. Association of the genotype with response rate, tumor shrinkage, median progression-free survival (mPFS), and median overall survival (mOS) was studied.Results
We collected clinical data from 154 patients with available germline DNA. Baseline prognostic markers were well-balanced between both subgroups. Patients with the TT genotype had a poorer outcome compared with patients with the CT/CC genotype. The median shrinkage of selected tumor target lesions during treatment with sunitinib was ?16% versus ?31% (P = .002), mPFS was 8 versus 15 months (P = .0007), and mOS was 22 versus 33 months (P = .04), respectively. On multivariate analysis, rs2981582 remained an independent predictor of PFS (hazard ratio, 2.858; 95% confidence interval, 1.659-4.923; P < .0001) and OS (hazard ratio, 1.795; 95% confidence interval, 1.003-3.212; P = .049).Conclusion
Polymorphism rs2981582 in FGFR2 is correlated to PFS and OS in patients with mccRCC treated with sunitinib. Prospective validation of the impact of this SNP is warranted. 相似文献7.
Jose M. Pacheco Dexiang Gao Derek Smith Thomas Purcell Mark Hancock Paul Bunn Tyler Robin Arthur Liu Sana Karam Laurie Gaspar Brian Kavanagh Chad Rusthoven Dara Aisner Robert Doebele D. Ross Camidge 《Journal of thoracic oncology》2019,14(4):691-700
Introduction
Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail.Methods
Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS.Results
Of the 110 patients with ALK-positive NSCLC who were identified, 105 received crizotinib as their initial ALK inhibitor. With a median follow-up time of 47 months, the median OS time from diagnosis of stage IV disease was 81 months (6.8 years). Brain metastases at diagnosis of stage IV disease (hazard ratio = 1.01, p = 0.971) and year of stage IV presentation (p = 0.887) did not influence OS. More organs with tumor at diagnosis of stage IV disease was associated with worse OS (HR = 1.49 for each additional organ with disease, including the CNS [p = 0.002]). Each additional month of pemetrexed-based therapy was associated with a 7% relative decrease in risk of death.Conclusion
Patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes. 相似文献8.
Morgan R.L. Lichtenstein Ryan D. Nipp Alona Muzikansky Kelly Goodwin Danyon Anderson Richard A. Newcomb Justin F. Gainor 《Journal of thoracic oncology》2019,14(3):547-552
Introduction
Immunotherapy has revolutionized the treatment of NSCLC, but little is known about the activity of programmed cell death 1 and programmed death ligand 1 blockade across age groups.Methods
We retrospectively evaluated patients with NSCLC who initiated programmed cell death 1 and programmed death ligand 1 inhibitors from January 2013 through July 2017. Medical records and radiographic imaging were reviewed to determine progression-free survival (PFS) and overall survival (OS). We also compared immunotherapy-related toxicities, steroid use, and hospitalizations by age.Results
Of the 245 patients, 26.1% were younger than 60 years, 31.4% were age 60 to 69 years, 31.0% were age 70 to 79 years, and 11.4% were age 80 years or older. The median PFS times by age group were as follows: younger than 60 years, 1.81 months; age 60 to 69 years, 2.53 months; age 70 to 79 years, 3.75 months; and age 80 years or older, 1.64 months (log-rank p value = 0.055). The median OS times by age group were as follows: younger than 60 years, 13.01 months; age 60 to 69 years, 14.56 months; age 70 to 79 years, 12.92 months; and age 80 years or older, 3.62 months (log-rank p value = 0.011). Rates of immunotherapy-related toxicities, steroid use, and hospitalizations did not differ by age.Conclusions
Although the OS and PFS benefits of immunotherapy differ by age, the rates of toxicity are similar regardless of age. 相似文献9.
Ieva Kurilova Regina G.H. Beets-Tan Jessica Flynn Mithat Gönen Gary Ulaner Elena N. Petre F. Edward Boas Etay Ziv Hooman Yarmohammadi Elisabeth G. Klompenhouwer Andrea Cercek Nancy A. Kemeny Constantinos T. Sofocleous 《Clinical colorectal cancer》2019,18(1):8-18
Introduction
The purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS.Materials and Methods
Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, as well as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling.Results
Patients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06).Conclusion
The developed nomogram included 6 pre-RAE parameters and provided good prediction of survival post-RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS. 相似文献10.
Jessica J. Lin Ginger Y. Jiang Nencyben Joshipura Jennifer Ackil Subba R. Digumarthy Sandra P. Rincon Beow Y. Yeap Justin F. Gainor Alice T. Shaw 《Journal of thoracic oncology》2019,14(4):683-690
Background
Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases.Methods
In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.Results
Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%–92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%–100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months–not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%–90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%–100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months–not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy.Conclusions
Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases. 相似文献11.
Jean-Louis Pujol Laurent Greillier Clarisse Audigier-Valette Denis Moro-Sibilot Lionel Uwer José Hureaux Florian Guisier Delphine Carmier Jeannick Madelaine Josiane Otto Valérie Gounant Patrick Merle Pierre Mourlanette Olivier Molinier Aldo Renault Audrey Rabeau Martine Antoine Marc G. Denis Pierre-Jean Souquet 《Journal of thoracic oncology》2019,14(5):903-913
Introduction
This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy.Methods
Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O’Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders.Results
Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).Conclusions
Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed. 相似文献12.
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13.
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14.
Paola Morelato Assunção Tamires Prates Lana Márcia Torresan Delamain Gislaine Oliveira Duarte Roberto Zulli Irene Lorand-Metze Carmino Antonio de Souza Erich Vinicius de Paula Katia Borgia Barbosa Pagnano 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):162-166
Background
Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors.Patients and Methods
We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively.Results
The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality.Conclusion
CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk. 相似文献15.
Bernardo Cacho-Díaz Héctor Spínola-Maroño Nancy Reynoso Alberto González-Aguilar Alejandro Mohar-Betancourt 《Clinical breast cancer》2019,19(2):e394-e398
Introduction
Breast cancer (BC) is the most common cancer in women, and the incidence of brain metastasis (BM) from BC ranges from 20% to 30%, with a median survival of 10 to 15 months. Previous reports have shown that the presence of obesity or diabetes negatively impacts survival. The present study investigates the association between obesity or diabetes mellitus (DM) and overall survival of patients with BC with BM.Materials and Methods
A database from 2 referral centers for the period of July 2014 to February 2018 was analyzed. The inclusion criteria were as follows: patients who had a confirmed diagnosis of BC with BM were followed and treated at these centers. Demographic data, body weight and height, clinical and oncologic history, functional status, prognostic scales, and prognoses were examined.Results
A total of 228 patients were included. The median age at BM was 50 years; the median survival after diagnosis was 12.1 months; 108 patients had a body mass index (BMI) ≥ 25, and 40 (17%) patients had DM. The association between survival and the presence of BMI > 25 exhibited a P value of 0.3.Discussion
We found no association between overweight, obesity, or DM and survival in patients with BC with BM. The role of obesity in cancer is a robust research topic, as there are many questions to be answered.Conclusion
Obesity as a prognostic indicator should be further studied, because we found no association between overall survival and either patients with BM from BC with a BMI > 25 or those with normal weight. 相似文献16.
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17.
Sonja Adebahr Marlene Hechtner Nele Schräder Tanja Schimek-Jasch Klaus Kaier Viola Duncker-Rohr Eleni Gkika Felix Momm Jan Gaertner Gerhild Becker Anca-Ligia Grosu Ursula Nestle 《Journal of thoracic oncology》2019,14(3):408-419
Introduction
Quality of life (QoL) of comorbid patients with pulmonary malignancies is a key issue in considering fractionated stereotactic body radiotherapy (SBRT) indication. This study investigates the early impact of SBRT on QoL.Methods
One hundred patients with pulmonary lesions were treated with SBRT from February 2011 to December 2014 within the prospective, monocenter, phase II STRIPE trial. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core module (EORTC QLQ-C30) and the QLQ-LC13 lung cancer-specific questionnaire were used to evaluate QoL before, 2 and 7 weeks after SBRT, then every 3 months for 2 years. We report on the analysis of early changes from baseline to 7-week follow-up exam. Impact of patient- and treatment-related factors on the change in QoL was analyzed.Results
QoL was assessed in 97 patients; compliance was 92% and 85% at baseline and 7 weeks after SBRT, respectively. No clinically relevant changes greater than or equal to 10 in the QoL/global health status (GHS), function scores and inquired symptoms were observed. Patients with baseline QoL below the median showed clinically relevant improvement in QoL/GHS (Δ16.7 ± 25.3, p = 0.003), emotional function (Δ14.4 ± 25.4, p = 0.013), and fatigue (Δ -10.1 ± 26.5, p = 0.089) in contrast to patients with high initial scores. No changes were observed in the dichotomized subgroups of initial Karnofsky index, Charlson Comorbidity Index, age, diagnosis, and tumor localization.Conclusions
In short-term follow-up, QoL is well maintained after pulmonary SBRT. Especially patients with low initial QoL/GHS scores show benefit from SBRT with respect to QoL. 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.
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20.
I. Alex Bowman Alisha Bent Tri Le Alana Christie Zabi Wardak Yull Arriaga Kevin Courtney Hans Hammers Samuel Barnett Bruce Mickey Toral Patel Tony Whitworth Strahinja Stojadinovic Raquibul Hannan Lucien Nedzi Robert Timmerman James Brugarolas 《Clinical genitourinary cancer》2019,17(2):e263-e272