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1.
Ibiayi Dagogo-Jack Hayley Robinson Mari Mino-Kenudson Anna F. Farago Vashine Kamesan A. John Iafrate Alice T. Shaw Jochen K. Lennerz 《Journal of thoracic oncology》2019,14(5):835-843
Introduction
Lung cancer patients with tumors harboring actionable alterations can achieve very durable responses to first-line targeted therapy. However, identifying targetable alterations using next-generation sequencing (NGS) is a complex and time-intensive process. As actionable genetic alterations are enriched in lung cancers arising in patients with limited smoking history, we designed a workflow to expedite NGS testing for this group.Methods
We developed a protocol to allow for next-day extraction of nucleic acids from frozen tissue. Specimens were designated as high priority during sequencing. We determined the interval between biopsy and NGS results to evaluate whether the workflow reduced the pre-analytical period and in-laboratory turnaround time and allowed for rapid initiation of genotype-matched therapy.Results
Between January 2017 and May 2018, 21 patients participated in the expedited sequencing program. The median interval between biopsy and NGS results was 10.7 days. Six patients received results within 1 week of biopsy. Performing molecular analysis on frozen tissue and prioritizing sequencing and analysis of these specimens reduced the pre-analytical period from 3.5 to 1.3 days (p < 0.0001) and shortened in-laboratory turnaround time by 3 days (11.8 versus 8.4 business days, p < 0.0001). Ninety-three percent of patients with an actionable molecular alteration received first-line targeted therapy. The median time-to-initiation of treatment was 19.7 days from biopsy.Conclusions
Sequencing and analyzing nucleic acids from frozen tissue is a practical strategy for shortening the time to matched therapy. The significant advantage of upfront treatment with targeted therapies in subsets of lung cancer patients provides rationale for developing workflows that accelerate comprehensive molecular analysis. 相似文献2.
Jon Zugazagoitia Daniel Rueda Nuria Carrizo Ana Belen Enguita David Gómez-Sánchez Asunción Díaz-Serrano Elisabeth Jiménez Antonio Mérida Rosa Calero Ricardo Lujan Eduardo De Miguel Pablo Gámez Vicente Díaz-Hellín Juan Antonio Nuñez Lara Iglesias Irene Ferrer Luis Paz-Ares Santiago Ponce-Aix 《Clinical lung cancer》2018,19(1):65-73.e7
Introduction
A substantial fraction of non–small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.Patients and Methods
After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs.Results
We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials.Conclusion
The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments. 相似文献3.
Clotilde Descarpentries Frédéric Leprêtre Fabienne Escande Zoulika Kherrouche Martin Figeac Shéhérazade Sebda Simon Baldacci Valérie Grégoire Philippe Jamme Marie-Christine Copin David Tulasne Alexis B. Cortot 《Journal of thoracic oncology》2018,13(12):1873-1883
Introduction
Genomic alterations affecting splice sites of MNNG HOS transforming gene (MET) exon 14 were recently identified in NSCLC patients. Objective responses to MET tyrosine kinase inhibitors have been reported in these patients. Thus, detection of MET exon 14 splice site mutations represents a major challenge. So far, most of these alterations were found by full-exome sequencing or large capture-based next-generation sequencing (NGS) panels, which are not suitable for routine diagnosis.Methods
Aiming to provide a molecular testing method applicable in routine practice, we first developed a fragment-length analysis for detecting deletions in introns flanking MET exon 14. Second, we designed an optimized targeted NGS panel called CLAPv1, covering the MET exon 14 and flanking regions in addition to the main molecular targets usually covered in genomic testing. In patients with MET exon 14 mutations, MET gene amplification, gene copy number and MET receptor expression were also determined.Results
Among 1514 formalin-fixed paraffin-embedded NSCLC samples, nonoptimized NGS allowed detection of MET exon 14 mutations in only 0.3% of the patients, and fragment length analysis detected deletions in 1.1% of the patients. Combined, the optimized CLAPv1 panel and fragment-length analysis implemented for routine molecular testing revealed MET exon 14 alterations in 2.2% of 365 additional NSCLC patients. MET gene amplification or high gene copy number was observed in 6 of 30 patients (20%) harboring MET exon 14 mutations.Conclusions
These results show that optimized targeted NGS and fragment-length analysis improve detection of MET alterations in routine practice. 相似文献4.
5.
Ibiayi Dagogo-Jack Marguerite Rooney Rebecca J. Nagy Jessica J. Lin Emily Chin Lorin A. Ferris Jennifer Ackil Jochen K. Lennerz Richard B. Lanman Justin F. Gainor Alice T. Shaw 《Journal of thoracic oncology》2019,14(5):816-824
Introduction
Circulating tumor DNA analysis is an emerging genotyping strategy that can identify tumor-specific genetic alterations in plasma including mutations and rearrangements. Detection of ROS1 fusions in plasma requires genotyping approaches that cover multiple breakpoints and target a variety of fusion partners. Compared to other molecular subsets of NSCLC, experience with detecting ROS1 genetic alterations in plasma is limited.Methods
To describe the spectrum of ROS1 fusions in NSCLC and determine sensitivity for detecting ROS1 fusions in plasma, we queried the Guardant Health plasma dataset and an institutional tissue database and compared plasma findings to tissue results. In addition, we used the Guardant360 NGS assay to detect potential genetic mediators of resistance in plasma from patients with ROS1-positive NSCLC who were relapsing on crizotinib.Results
We detected seven distinct fusion partners in plasma, most of which (n = 6 of 7) were also represented in the tissue dataset. Fusions pairing CD74 with ROS1 predominated in both cohorts (plasma: n = 35 of 56, 63%; tissue: n = 26 of 52, 50%). There was 100% concordance between the specific tissue- and plasma-detected ROS1 fusion for seven patients genotyped with both methods. Sensitivity for detecting ROS1 fusions in plasma at relapse on ROS1-directed therapy was 50%. Six (33%) of 18 post-crizotinib plasma specimens harbored ROS1 kinase domain mutations, five of which were ROS1 G2032R. Two (11%) post-crizotinib plasma specimens had genetic alterations (n = 1 each BRAF V600E and PIK3CA E545K) potentially associated with ROS1-independent signaling.Conclusions
Plasma genotyping captures the spectrum of ROS1 fusions observed in tissue. Plasma genotyping is a promising approach to detecting mutations that drive resistance to ROS1-directed therapies. 相似文献6.
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7.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献8.
Sean P. Stoy Jeremy P. Segal Jeffrey Mueller Larissa V. Furtado Everett E. Vokes Jyoti D. Patel Septimiu Murgu 《Clinical lung cancer》2018,19(3):230-238.e2
Introduction
Next generation sequencing (NGS) testing of lung cancer is recommended by guidelines, and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) often provides the only material available for testing. Previous studies have demonstrated successful NGS testing on cell block samples obtained by EBUS; however, cytology smears provide a more reliable sample with better DNA quality for testing. In this study, we aimed to determine the success rate of OncoScreen (50 gene) and OncoPlus (1213 gene) panel NGS testing of cytology samples obtained by EBUS utilizing 22- and 25-gauge needles.Methods
Fifty-four patients underwent EBUS-TBNA of lung cancer for which NGS testing was requested. Data was analyzed for needle gauge, cytologic assessment, NGS test success, and sample type (cytology smear or cell block) used for testing.Results
Eighty-five NGS tests were ordered on 54 samples. Overall, 95.3% of samples had successful testing. OncoScreen and OncoPlus panels were successful 98.0% and 91.4% of the time, respectively. Cytology smears provided testing material for 85% of the tests. OncoScreen testing was successful in 97.5% and 100% of the 22- and 25-gauge samples, respectively (P = 1.00). OncoPlus testing was successful in 91.3% and 100% of the 22- and 25-gauge samples, respectively (P = 1.00).Conclusions
NGS can be reliably performed on cytology smears obtained from EBUS-TBNA. The size of the needle does not seem to affect the success rate of small or large panel NGS tests. 相似文献9.
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10.
Alexa B. Schrock Allison Welsh Jon H. Chung Dean Pavlick Eric H. Bernicker Benjamin C. Creelan Brady Forcier Jeffrey S. Ross Philip J. Stephens Siraj M. Ali Ibiayi Dagogo-Jack Alice T. Shaw Tianhong Li Sai-Hong Ignatius Ou Vincent A. Miller 《Journal of thoracic oncology》2019,14(2):255-264
Introduction
Genomic profiling informs selection of matched targeted therapies as part of routine clinical care in NSCLC. Tissue biopsy is the criterion standard; however, genomic profiling of blood-derived circulating tumor DNA (ctDNA) has emerged as a minimally invasive alternative.Methods
Hybrid capture–based genomic profiling of 62 genes was performed on blood-based ctDNA from 1552 patients with NSCLC.Results
Evidence of ctDNA was detected in 80% of samples, and in 86% of these cases, at least one reportable genomic alteration (GA) was detected. Frequently altered genes were tumor protein p53 gene (TP53) (59%), EGFR (25%), and KRAS (17%). Comparative analysis with a tissue genomic database (N = 21,500) showed similar frequencies of GAs per gene, although KRAS mutation and EGFR T790M were more frequent in tissue and ctDNA, respectively (both p < 0.0001), likely reflecting the use of liquid versus tissue biopsy after relapse during targeted therapy. In temporally matched ctDNA and tissue samples from 33 patients with evidence of ctDNA in their blood, 64% of GAs detected in tissue were also detected in ctDNA, including 78% of short variants (58 of 74) and 100% of rearrangements (four of four), but only 16% of amplifications (four of 25).Conclusions
Genomic profiling of ctDNA detected clinically relevant GAs in a significant subset of NSCLC cases. Most alterations detected in matched tissue were also detected in ctDNA. These results suggest the utility of ctDNA testing in advanced NSCLC as a complementary approach to tissue testing. Blood-based ctDNA testing may be particularly useful at the time of progression during targeted therapy. 相似文献11.
Chien-Hua Tseng Ben-Jei Tsuang Chun-Ju Chiang Kai-Chen Ku Jeng-Sen Tseng Tsung-Ying Yang Kuo-Hsuan Hsu Kun-Chieh Chen Sung-Liang Yu Wen-Chung Lee Tsang-Wu Liu Chang-Chuan Chan Gee-Chen Chang 《Journal of thoracic oncology》2019,14(5):784-792
Introduction
For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM2.5) levels on LC in Taiwan, in relation to contrasting PM2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).Methods
We reviewed 371,084 patients with LC to assess smoking prevalence and correlations between the incidence of adenocarcinoma lung cancer (AdLC) and non-AdLC. Two subsets were selected to assess different AdLC stage trends and the effect of PM2.5 on survival of patients with AdLC.Results
From 1995 to 2015, the proportion of male adult ever-smokers decreased from 59.4% to 29.9% whereas the female smoking rate remained low (3.2% to 5.3%). AdLC incidence in males and females increased from 9.06 to 23.25 and 7.05 to 24.22 per 100,000 population, respectively. Since 1993, atmospheric visibility in NT improved (from 7.6 to 11.5 km), but deteriorated in ST (from 16.3 to 4.2 km). The annual percent change in AdLC stages IB to IV was 0.3% since 2009 (95% confidence interval [CI]: -1.9%–2.6%) in NT, and 4.6% since 2007 (95% CI: 3.3%–5.8%) in ST; 53% patients with LC had never smoked. Five-year survival rates for never-smokers, those with EGFR wild-type genes, and female patients with AdLC were 12.6% in NT and 4.5% in ST (hazard ratio: 0.79, 95% CI: 0.70–0.90).Conclusions
In Taiwan, greater than 50% of patients with LC had never smoked. PM2.5 level changes can affect AdLC incidence and patient survival. 相似文献12.
13.
Stephanie R. Rice Jason K. Molitoris Melissa A.L. Vyfhuis Martin J. Edelman Whitney M. Burrows Josephine Feliciano Elizabeth M. Nichols Mohan Suntharalingam James Donahue Shamus R. Carr Joseph Friedberg Shahed Badiyan Charles B. Simone Steven J. Feigenberg Pranshu Mohindra 《Clinical lung cancer》2019,20(1):e107-e114
Background
We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non–small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases.Materials and Methods
A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed.Results
The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009).Conclusion
Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients. 相似文献14.
Wellington F. da Silva Lidiane Inês da Rosa Gabriel Lacerda Marquez Lucas Bassolli Luciana Tucunduva Douglas Rafaele Almeida Silveira Valeria Buccheri Israel Bendit Eduardo Magalhães Rego Vanderson Rocha Elvira D.R.P. Velloso 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(2):e116-e122
Introduction
Although a considerable improvement in survival of patients with acute promyelocytic leukemia (APL) has been seen over the past decades, real-life outcomes seem to be worse than those reported by prospective studies. We aim to describe clinical characteristics and outcomes of adult patients diagnosed with APL in an academic hospital from the University of Sao Paulo.Patients and Methods
We retrospectively reviewed the medical charts of 61 patients with APL diagnosed between January 2007 and May 2017. Baseline clinical features and follow-up data were collected, focusing on early toxicity variables such as infection, bleeding, and thrombosis in the first 30 days from diagnosis.Results
Among the 61 patients with APL, 54 received any chemotherapy. All patients also received all-trans retinoic acid (ATRA). Bleeding events were the main cause of death before receiving chemotherapy. Most patients belonged to the intermediate (43%) and high-risk (41%) groups, according to Sanz score. The ‘7 + 3 + ATRA’ regimen was the most used regimen (n = 38). An early death rate of 20% was found, predominantly owing to sepsis. After a median follow-up of 5 years, only 1 relapse was diagnosed. The overall survival at 5 years was 59%.Discussion
In comparison with prospective trials with ATRA-based regimens, we found an inferior overall survival, mostly on account of a high early-death rate. Our results are in line with other real-life retrospective reports published in the past decades.Conclusion
Results of real-life studies differ from those found by prospective trials. Accordingly, early actions and supportive care are still needed, aiming to decrease toxicity, especially in developing countries. 相似文献15.
Tony Li Ranjeeta Mallick Arleigh McCurdy Sunita Mulpuru Lothar Huebsch Chris Bredeson David Allan Natasha Kekre 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(2):68-72
Introduction
Despite the risk of morbidity and mortality associated with autologous hematopoietic cell transplantation (ASCT), there are no clear guidelines as to how to screen for these risks. This study sought to determine the utility of pulmonary function tests (PFTs) prior to ASCT on predicting posttransplant clinical outcomes.Patients and Methods
Patients undergoing ASCT between 2010 and 2012 at the Ottawa Hospital (n = 172) were reviewed. PFT results prior to ASCT were retrieved. The primary outcomes were incidence of intensive care unit (ICU) admission, Seattle Criteria for pulmonary toxicities, and transplant-related mortality (TRM).Results
PFTs were performed for 91 (53%) patients prior to ASCT. There were more smokers in the PFT cohort than the non-PFT cohort (41.8% vs. 19.8%, respectively; P < .0001). Pulmonary toxicity as measured by the Seattle Criteria did not correlate with PFT results (normal vs. abnormal, 8.1% and 6.1%, respectively; P = 1.00). There were no differences in incidence of ICU admission by PFT result (normal vs. abnormal, 2.7% vs. 8.2%, respectively; P = .61) and no difference in TRM by PFT result (normal vs. abnormal, 0% vs. 2.0%, respectively; P = 1.00).Conclusion
Despite testing patients deemed higher risk for pulmonary toxicity, abnormal PFTs did not predict for an increased risk of pulmonary toxicity, ICU admission, or TRM at our center. 相似文献16.
Cécile Vicier Lillian Werner Jonathan Chipman Lauren C. Harshman Dattatraya H. Patil Raina N. Fichorova Jennifer R. Rider Martin G. Sanda Lorelei A. Mucci Christopher J. Sweeney 《Clinical genitourinary cancer》2019,17(1):32-37
Background
Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.Patients and Methods
Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis.Results
A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer.Conclusion
Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer. 相似文献17.
Shuning Ding Jiayi Wu Caijin Lin Weiguo Chen Yafen Li Kunwei Shen Li Zhu 《Clinical breast cancer》2019,19(1):e66-e73
Background
Pure mucinous breast cancer (PMBC) is a rare pathologic type of breast cancer, the prognostic factors of which have not been clearly defined. This study aimed to analyze the prognostic markers and distribution of 21-gene recurrence score (RS) in patients with PMBC.Patients and Methods
Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a retrospective analysis of PMBC cases was conducted. Multivariate analyses were used to evaluate the indicators for prognosis and the correlations between RS and traditional clinicopathologic characteristics. Disease was subdivided into 4 molecular phenotypes using estrogen receptor (ER) status and tumor grade.Results
Of the 8048 patients, most had ER-positive and node-negative tumors. Multivariate analysis revealed that molecular phenotype as well as age, race, tumor size, and lymph node status was an independent prognostic factor for patients with PMBC (P < .05). The 5-year breast cancer–specific survival of patients among different phenotypes was significantly different (97.9% for ER-positive and grade I tumor, 96.9% for ER-positive and grade II-III tumor, 96% for ER-negative and grade I tumor, 90.1% for ER-negative and grade II-III tumors, P < .001). The proportions of patients categorized into low, intermediate, and high RS risk group were 64.9%, 31.9%, and 3.2%, respectively. Grade, progesterone receptor status, and age were identified as independent variables associated with RS.Conclusion
PMBC had favorable biological features and relatively good prognosis. Molecular phenotype as well as age, race, tumor size, and lymph node status were independent prognostic markers. Furthermore, age, progesterone receptor status, and grade could independently predict RS. 相似文献18.
Geoffrey Alan Watson Oana Deac Razia Aslam Richard O&#x;Dwyer Antonia Tierney Sue Sukor John Kennedy 《Clinical breast cancer》2019,19(1):e186-e194
Background
The cyclin-dependent kinase 4/6 inhibitor palbociclib has emerged as a novel therapeutic agent in metastatic breast cancer. Neutropenia is commonly observed, and thus stringent treatment guidelines regarding complete blood count (CBC) monitoring have been developed. The aim of this study was to provide a real-world experience of the toxicities associated with palbociclib therapy and to evaluate compliance with CBC monitoring.Patients and Methods
We performed a retrospective single-center audit of hormone receptor–positive metastatic breast cancer patients treated with palbociclib over a 6-month period in an Irish tertiary referral hospital.Results
A total of 64 patients were included in the analysis. Palbociclib was most commonly used in combination with letrozole (n = 40). A total of 28 patients (44%; 95% confidence interval, 31.2-56.2) had treatment deferrals due to neutropenia, with a median time to first deferral of 4 weeks. Fifteen patients (23%; 95% confidence interval, 15.4-37.7) required dose adjustments; however, there was no association with an increased risk of progressive disease (P = .56). Only 3 patients discontinued treatment as a result of poor tolerance. Adverse events were as expected; however, 7 venous thromboembolic events were reported.Conclusion
Compliance was good with existing CBC monitoring guidelines. We observed an 11% incidence of venous thromboembolic events, a significant increase from 2% reported in the PALOMA-3 trial. Further studies are recommended to determine if prophylactic anticoagulation may benefit these patients. 相似文献19.
Sebastiano Nazzani Felix Preisser Elio Mazzone Michele Marchioni Marco Bandini Zhe Tian Francesco A. Mistretta Shahrokh F. Shariat Denis Soulières Emanuele Montanari Pietro Acquati Alberto Briganti Luca Carmignani Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(1):e97-e103