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1.
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
Background
Brain metastases (BM) occur frequently in patients with metastatic kidney cancer and are a significant source of morbidity and mortality. Although historically associated with a poor prognosis, survival outcomes for patients in the modern era are incompletely characterized. In particular, outcomes after adjusting for systemic therapy administration and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors are not well-known.Patients and Methods
A retrospective database of patients with metastatic renal cell carcinoma (RCC) treated at University of Texas Southwestern Medical Center between 2006 and 2015 was created. Data relevant to their diagnosis, treatment course, and outcomes were systematically collected. Survival was analyzed by the Kaplan-Meier method. Patients with BM were compared with patients without BM after adjusting for the timing of BM diagnosis, either prior to or during first-line systemic therapy. The impact of stratification according to IMDC risk group was assessed.Results
A total of 56 (28.4%) of 268 patients with metastatic RCC were diagnosed with BM prior to or during first-line systemic therapy. Median overall survival (OS) for systemic therapy-naive patients with BM compared with matched patients without BM was 19.5 versus 28.7 months (P = .0117). When analyzed according to IMDC risk group, the median OS for patients with BM was similar for favorable- and intermediate-risk patients (not reached vs. not reached; and 29.0 vs. 36.7 months; P = .5254), and inferior for poor-risk patients (3.5 vs. 9.4 months; P = .0462). For patients developing BM while on first-line systemic therapy, survival from the time of progression did not significantly differ by presence or absence of BM (11.8 vs. 17.8 months; P = .6658).Conclusions
Survival rates for patients with BM are significantly better than historical reports. After adjusting for systemic therapy, the survival rates of patients with BM in favorable- and intermediate-risk groups were remarkably better than expected and not statistically different from patients without BM, though this represents a single institution experience, and numbers are modest. 相似文献2.
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3.
Bo Lan Fei Ma Mei Han Shanshan Chen Wenna Wang Qiao Li Ying Fan Yang Luo Ruigang Cai Jiayu Wang Peng Yuan Pin Zhang Qing Li Binghe Xu 《Clinical breast cancer》2019,19(2):e370-e375
Introduction
UGT1A4 is a major enzyme responsible for the glucuronidation of tamoxifen (TAM) and its metabolites. Genetic variations in the UGT1A4 gene could have a significant impact on the clinical efficacy of TAM. This study was performed to validate the association between UGT1A4 polymorphisms and the clinical outcomes for patients with breast cancer who received adjuvant TAM.Patients and Methods
A total of 773 patients with breast cancer who received adjuvant TAM (n = 321) or aromatase inhibitors (n = 452) at the National Cancer Center in China were analyzed. Through a series of screenings, the single nucleotide polymorphism rs869283 (c.-1180G>A) in the promoter region of the UGT1A4 gene was selected. The associations of rs869283 genotype with disease-free survival (DFS) and clinicopathologic characteristics were analyzed.Results
A total of 608 (78.7%) patients were wild-type G/G genotype, 154 (19.9%) patients were G/A genotype, and 11 (1.4%) patients were A/A genotype. In the TAM treatment group, patients with A/A or G/A genotype had a lower 5-year DFS rate than those with the wild-type G/G genotype (69.3% vs. 83.7%; P = .031). The rs869283 genotype remained an independent prognostic marker for DFS in multivariate analysis (hazard ratio, 1.74; P = .014). No association between the rs869283 genotype and DFS was found in patients who received AIs (P = .772).Conclusions
Our findings showed that patients with the UGT1A4 rs869283 G/A or A/A genotype received less benefit from adjuvant TAM treatment than those with the G/G genotype. Further studies are warranted to confirm our findings. 相似文献4.
Alvaro Quintanal-Villalonga Sonia Molina-Pinelo Cristina Cirauqui Laura Ojeda-Márquez Ángela Marrugal Rocío Suarez Esther Conde Santiago Ponce-Aix Ana Belén Enguita Amancio Carnero Irene Ferrer Luis Paz-Ares 《Journal of thoracic oncology》2019,14(4):641-655
Introduction
There is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma.Methods
We performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogate and interaction assays. We performed monotherapy and combination EGFR/FGFR inhibitor sensitivity assays in vitro and in vivo in cell line– and patient-derived xenografts. We determined FGFR1 mRNA expression in a cohort of patients with anti–EGFR therapy–treated adenocarcinoma.Results
We have reported a cooperative interaction between FGFR1 and EGFR in this context, resulting in increased EGFR activation and oncogenic signaling. We have provided in vitro and in vivo evidence indicating that FGFR1 expression increases tumorigenicity in cells with high EGFR activation in EGFR-mutated and EGFR wild-type models. At the clinical level, we have shown that high FGFR1 expression levels predict higher resistance to erlotinib or gefitinib in a cohort of patients with tyrosine kinase inhibitor–treated EGFR-mutated and EGFR wild-type lung adenocarcinoma. Dual EGFR and FGFR inhibition in FGFR1-overexpressing, EGFR-activated models shows synergistic effects on tumor growth in vitro and in cell line– and patient-derived xenografts, suggesting that patients with tumors bearing these characteristics may benefit from combined EGFR/FGFR inhibition.Conclusion
These results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR inhibitors for selected patients with increased FGFR1 overexpression and EGFR activation. 相似文献5.
Baoan Hong Lin Cai Jiangyi Wang Shengjie Liu Jingcheng Zhou Kaifang Ma Jiufeng Zhang Bowen Zhou Xiang Peng Ning Zhang Kan Gong 《Clinical genitourinary cancer》2019,17(2):97-104.e1
Background
Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.Patients and Methods
Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry. Correlations between PD-L1 expression and clinicopathological features were analyzed.Results
In sporadic ccRCC, the positive expression rate of PD-L1 was 47.3% (61/129). Positive PD-L1 expression was correlated with advanced tumor T stage (P = .011), higher Fuhrman nuclear grade (P = .022), poor disease-free survival (P = .037), and sex (P = .025). In the VHL-associated hereditary ccRCC, positive PD-L1 expression rate was 34.6% (9/26), lower than that in sporadic ccRCC. Positive PD-L1 was correlated with higher Fuhrman nuclear grade (P = .008), but not with sex, age, tumor stage, or the onset age of VHL-associated tumors.Conclusion
Positive PD-L1 expression was correlated with the aggressive clinicopathological features in sporadic and VHL-associated hereditary ccRCC. Whether PD-L1 expression level in ccRCC is related to the effectiveness of programmed death-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated. 相似文献6.
Elio Mazzone Felix Preisser Sebastiano Nazzani Zhe Tian Nicola Fossati Giorgio Gandaglia Andrea Gallina Denis Soulieres Derya Tilki Francesco Montorsi Shahrokh F. Shariat Fred Saad Alberto Briganti Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(2):105-113.e2
Background
Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM.Patients and Methods
Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs.Results
Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P < .001), and overall mortality–free survival was 12 versus 7 months (P < .001) for, respectively, RC and non-RC patients. In multivariable CRMs, lower CSM (hazard ratio = 0.48; P < .001) and lower overall mortality (hazard ratio = 0.49; P < .001) rates were recorded in RC patients. LND status did not affect CSM-free survival (13 vs. 10 months; P = .1). Cubic splines-derived cutoff of ≥ 13 number of removed nodes showed better CSM-free survival (20 vs. 11 months; P = .02) and reduced CSM in CRMs (hazard ratio = 0.67; P = .02).Conclusion
Our study validates the survival benefit of RC in mUCB and highlights the importance of more extensive LND. These findings may corroborate the hypothesis of potential cytoreductive effect of surgery in the context of metastatic disease. 相似文献7.
Ryuma Tokunaga Shu Cao Madiha Naseem Jae Ho Lo Francesca Battaglin Alberto Puccini Martin D. Berger Shivani Soni Joshua Millstein Wu Zhang Sebastian Stintzing Fotios Loupakis Chiara Cremolini Volker Heinemann Alfredo Falcone Heinz-Josef Lenz 《Clinical colorectal cancer》2019,18(1):e8-e19
Background
Adenosine has an immunosuppressive and angiogenic modulation of the tumor microenvironment. The present study explored the efficacy of single nucleotide polymorphisms (SNPs) in adenosine-related molecules for patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy.Patients and Methods
We analyzed genomic DNA extracted from 451 samples from 3 independent cohorts: a discovery cohort of 107 patients treated with FOLFIRI (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab in FIRE-3 (ClinicalTrials.gov identifier, NCT00433927); a validation cohort of 215 patients with FOLFIRI plus bevacizumab in TRIBE (ClinicalTrials.gov identifier, NCT00719797); and a control cohort of 129 patients treated with FOLFIRI plus cetuximab in FIRE-3. The relationship between the selected SNPs and clinical outcomes was analyzed.Results
In the discovery cohort, patients with any C allele in CD39 rs11188513 had significantly shorter median progression-free survival compared with those with the T/T variant (11.3 vs. 13.1 months; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .022) on univariate analysis. Also, their overall survival (OS) was shorter (27.4 vs. 49.9 months; HR, 2.10; 95% CI, 1.07-4.10; P = .031) on univariate and multivariable analyses. The significant association between CD39 rs11188513 and OS was confirmed in the validation cohort (25.8 vs. 31.6 months; HR, 1.53; 95% CI, 1.09-2.15; P = .013). CD73 rs2229523 and A2BR rs2015353 in the discovery cohort and CD39 rs2226163 in the validation cohort showed significant correlations with OS on univariate and multivariable analyses. None of SNPs were significant in the cetuximab control cohort.Conclusion
Selected SNPs in the adenosine pathway could affect the clinical outcomes of patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab. 相似文献8.
Suzanne B. Merrill Brian S. Sohl Ashiya Hamirani Erik B. Lehman Kathleen K. Lehman Matthew G. Kaag Jay D. Raman 《Clinical genitourinary cancer》2019,17(2):132-138
Introduction
The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality.Patients and Methods
We identified 737 patients who underwent partial or radical nephrectomy for M0 RCC between 1998 and 2016. Overall survival and disease-specific survival stratified by the type of recurrence detection (asymptomatic vs. symptomatic) was estimated using Kaplan-Meier probabilities both from the time of surgery and from the time of recurrence. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on mortality.Results
A total of 78 patients (10.6%) experienced recurrence after surgery, of whom 63 (80.8%) were asymptomatic (detected using routine surveillance) and 15 (19.2%) were symptomatic. The median postoperative follow-up was 47.2 months (interquartile range, 26.3-89.4 months). Five- and 10-year overall survival, from time of surgery, among patients with asymptomatic versus symptomatic recurrences was 57% and 39% versus 24% and 8%, respectively (P = .0002). As compared with asymptomatic recurrences, patients with symptomatic recurrences had an increased risk of overall (OD) and disease-specific death (DSD) both when examined from the time of surgery (OD: hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.33-7.49; P = .0091 and DSD: HR, 3.44; 95% CI, 1.38-8.57; P = .0079) and from the time of recurrence (OD: HR, 2.93; 95% CI, 1.24-6.93; P = .0143 and DSD: HR, 3.62; 95% CI, 1.45-9.01; P = .0058).Conclusions
Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival. 相似文献9.
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10.
Yamila Goenaga Vázquez Fernando Cabanillas Joel Rivera Concepción Olga L. Díaz Miranda 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):e153-e158
Background
Although most cases of herpes zoster (HZ) are self-limited, lymphoma patients are at greater risk for recurrences and more serious and atypical complications that can delay scheduled anti-lymphoma treatment or prevent its continuation.Patients and Methods
This is a cohort study with a retrospective chart review of 415 patients diagnosed with lymphoma to determine the incidence and risk factors for developing HZ among this population. Data collected included date of diagnosis, patient’s age, last follow-up or death, stage and presentation of lymphoma, treatment type, baseline laboratory tests, and comorbidities. Patients with a diagnosis of HZ at any time during their course of illness were identified. Patients were divided into various subgroups to analyze their risk of developing HZ individually. The frequencies of each categorical variable were compared with χ2 tests. Relative risks were calculated using 95% confidence intervals (CIs).Results
During a median follow-up of 8.9 years, 46 cases of HZ were identified, with an overall incidence density of 11.1%. Higher rates of HZ were associated with lymphocytopenia (P = .038), presentation (P = .030), stage (P = .034), autologous stem cell transplant (P = .019), multiple courses of chemotherapy (P = .035), and fludarabine therapy (P = .002). Those who received what we labeled as ‘highly immunosuppressive chemotherapy’ had 2.9 times the risk to develop HZ than those who did not receive this therapy (95% CI, 1.47-5.623; P < .001).Conclusions
Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Patients with the risk factors described here might benefit from antiviral prophylaxis against HZ. 相似文献11.
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12.
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13.
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14.
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15.
Pashtoon Murtaza Kasi Faisal Shahjehan Jordan J. Cochuyt Zhuo Li Dorin Toma Colibaseanu Amit Merchea 《Clinical colorectal cancer》2019,18(1):e87-e95
Background
Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.Patients and Methods
This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear.Results
The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and right-sided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001).Conclusion
Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised. 相似文献16.
Heather A. Jacene Trisha Youn Pamela J. DiPiro Jiani Hu Su-Chun Cheng Yoko Franchetti Hina Shah Jennifer R. Bellon Laura Warren Emily Schlosnagle Faina Nakhlis Jennifer Rosenbluth Eren Yeh Beth Overmoyer 《Clinical breast cancer》2019,19(2):146-155
Background
The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS).Patients and Methods
Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage.Results
SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non–triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor.Conclusion
2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting. 相似文献17.
Manuela Vasconcelos Castro Sales Claudia K. Suemoto Daniel Apolinario ValeriaT. Serrao Celi S. Andrade David M. Conceição Edson Amaro Brian Alvarez Ribeiro de Melo Rachel P. Riechelmann 《Clinical colorectal cancer》2019,18(1):19-27
Purpose
Chemotherapy-related cognitive impairment can occur in cancer survivors after treatment, especially those patients who have undergone chemotherapy for breast cancer. The frequency and to what extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. The present prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC compared with a control group who had not undergone chemotherapy.Patients and Methods
Consecutive patients with localized stage II and III CRC completed neuropsychological assessments, self-reported cognitive complaint questionnaires, and depressive symptom evaluations before starting fluoropyrimidine-based adjuvant chemotherapy and after 12 months. Blood was collected for apolipoprotein E genotyping. Diffusion tensor imaging data were acquired from a subset of participants at both evaluation points.Results
From December 2012 to December 2014, 137 patients were approached and 85 were included. Of these 85 patients, 49 had undergone chemotherapy and 26 had not, in accordance with the standard recommendations for adjuvant therapy for CRC. The mean age was 62.5 ± 9.4 years, 60% were men, and the mean educational attainment was 7.6 ± 3.7 years. No difference was found in the global composite score (P = .38), attention (P = .84), or memory (P = .97) between the 2 groups during the follow-up period (mean ± standard deviation, 375 ± 29 days). However, a statistically significant difference was found for executive function after adjustment for age, sex, education, and depressive symptoms at baseline (β ?1.80; 95% confidence interval, ?3.50 to ?0.11; P = .04), suggesting worse performance for the chemotherapy group. For the 32 patients who had undergone magnetic resonance imaging, tract-based spatial statistics did not show voxelwise significant differences in structural brain connectivity at baseline or during follow-up. Apolipoprotein E polymorphisms were not predictive of cognitive dysfunction.Conclusion
Patients with CRC who received adjuvant 5-fluorouracil with or without oxaliplatin presented with a decline in executive function after 12 months compared with patients with localized disease who had not received chemotherapy. 相似文献18.
Arti Hurria Enrique Soto-Perez-de-Celis Suzette Blanchard Peggy Burhenn Christina Haeyoung Yeon Yuan Yuan Daneng Li Vani Katheria James Ross Waisman Thehang H. Luu George Somlo Anne M. Noonan Ty Lee Nimit Sudan Samuel Chung Arnold Rotter Anait Arsenyan Abrahm Levi Joanne E. Mortimer 《Clinical breast cancer》2019,19(2):89-96
Introduction
Phase II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-paclitaxel in older adults with metastatic breast cancer (MBC).Patients and Methods
Patients aged ≥ 65 years with MBC and ≤ 1 previous line of chemotherapy received 100 mg of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy, and the validated Cancer and Aging Research Group (CARG) chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student t tests, and the Fisher test. Response rate and progression-free survival were evaluated using the Kaplan-Meier method.Results
Forty patients (mean age, 73 years; range, 65-87 years) were included. The median number of cycles was 6, 75% (n = 30) of patients had ≥ 1 dose hold, and 50% (n = 20) had ≥ 1 dose reduction. Fifty-eight percent (n = 23) had treatment-related ≥ grade 3 toxicities, and 30% (n = 12) were hospitalized owing to toxicity. Thirty-five percent (n = 14) responded, and the median progression-free survival was 6.5 months (95% confidence interval, 5.5 months to undefined). Patients with intermediate/high toxicity risk scores had higher risk of grade ≥ 3 toxicity than those with low risk scores (odds ratio, 5.8; 95% confidence interval, 1.3-33.1; P = .01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations.Conclusions
Among older adults with MBC receiving weekly nab-paclitaxel, more than one-half experienced ≥ grade 3 chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability. 相似文献19.
Madeline Grade Julie Koenig Yushen Qian Navjot Sandhu Yufei Liu Brandon Turner Rie von Eyben Susan Knox Sara Dudley 《Practical radiation oncology》2019,9(2):e203-e209
Purpose
Emergent palliative radiation therapy (PRT) of symptomatic metastases can significantly increase the quality of life of patients with cancer. In some contexts, this treatment may be underused, but in others PRT may represent an excessively aggressive intervention. The characterization of the current use of emergent PRT is warranted for optimized value and patient-centered care.Methods and Materials
This study is a cross-sectional retrospective analysis of all emergent PRT courses at a single academic tertiary institution across 1 year.Results
A total of 214 patients received a total of 238 treatment courses. The most common indications were bone (39%) and brain (14%) metastases. Compared with outpatients, inpatients had lower mean survival rates (2 months vs 6 months; P < .001), higher rates of stopping treatment early (19.1% vs 9.0%; P = .034), and greater involvement of palliative care (44.8% vs 24.1%; P < .001), but the same mean planned fractions (9.10 vs 9.40 fractions; P = .669). In a multiple predictor survival analysis, palliative care involvement (P = .025), male sex (P = .001), ending treatment early (P = .011), and having 1 of 3 serious indications (airway compromise, leptomeningeal disease, and superior/inferior vena cava involvement; P = .007) were significantly associated with worse overall survival.Conclusions
Survival is particularly poor in patients who receive emergent PRT, and patient characteristics such as functional status and indication should be considered when determining fractionation schedule and dosing. A multi-institutional study of practice patterns and outcomes is warranted. 相似文献20.
Walker Mainwaring John Bowers Ngoc Pham Todd Pezzi Mihir Shukla Mark Bonnen Michelle Ludwig 《Clinical breast cancer》2019,19(2):e343-e351