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1.
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2.
Sungwoo Park Jae-Cheol Jo Young Rok Do Deok-Hwan Yang Sung-Nam Lim Won-Sik Lee Won Seog Kim Ho Sup Lee Dae-Sik Hong Hyo Jung Kim Ho-Jin Shin 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):149-156
Introduction
Elderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma.Patients and Methods
A total of 53 patients aged ≥ 65 years with diffuse large B-cell lymphoma diagnosed between August 2012 and December 2014 were enrolled onto this study. RD-R-CHOP regimen consisted of rituximab at 375 mg/m2, cyclophosphamide at 600 mg/m2, doxorubicin at 30 mg/m2, and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle.Results
The median follow-up duration was 18 months (range, 1-44 months). Complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free and overall survival rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively. Grade 3/4 neutropenia occurred in 20 patients (37.7%), while febrile neutropenia occurred in 7 patients (20.7%).Conclusion
Outcomes of RD-R-CHOP chemotherapy were comparable to those of standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy. In the future, strategies such as tailored therapy based on geriatric assessment results are needed to determine the chemotherapeutic dosage. 相似文献3.
M. Arunsingh S. Vaidyanathan K.E. Dyker M. Sen A.F. Scarsbrook R.J.D. Prestwich 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(4):212-218
Aim
There are few data to inform on the use of response assessment 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following radical radiotherapy without chemotherapy for head and neck squamous cell carcinoma (HNSCC). This retrospective study evaluated the accuracy of PET-CT in HNSCC following radical radiotherapy.Materials and methods
In total, 138 patients with HNSCC treated with radical radiotherapy without chemotherapy who underwent a baseline and response assessment FDG PET-CT were identified. FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes.Results
The median follow-up was 26 months. FDG-avid disease at baseline was present for the primary site and lymph nodes in 118 and 86 patients, respectively. With regard to the primary tumour, the negative predictive value (NPV) of a complete metabolic response (CMR) was 95%; the positive predictive value (PPV) of equivocal uptake and a positive scan were 6% and 82%, respectively. The likelihood ratios for a CMR, equivocal and positive scans of the primary site were 0.19, 0.22, 14.8, respectively. With regard to lymph node disease, the NPV of a CMR was 91%, the PPV of equivocal uptake and a positive scan were 33% and 88%, respectively. Likelihood ratios for lymph node disease for CMR, equivocal and positive scans were 0.19, 0.97 and 15.1, respectively.Conclusion
Compared with the accuracy reported in the literature following chemoradiotherapy, response assessment FDG PET-CT following radical radiotherapy without chemotherapy had a similarly high NPV, whereas the PPV following a positive scan was higher. 相似文献4.
Uday Yanamandra Prateek Deo Kamal Kant Sahu Ram Vasudevan Nampoothiri Nalini Gupta Anusree Prabhakaran Deb Prasad Dhibhar Alka Khadwal Gaurav Prakash Man Upadesh Singh Sachdeva Deepesh Lad Neelam Varma Subhash Varma Pankaj Malhotra 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):183-189.e1
Background
Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.Patients and Methods
In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes.Results
Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months.Conclusion
MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis. 相似文献5.
Yun Yi Tan Bahaa Al-Bubseeree David Irvine Graham MacDonald Grant McQuaker Anne Parker Ashita Waterston Jeff White 《Clinical genitourinary cancer》2019,17(2):125-131
Purpose
To report outcomes from high-dose chemotherapy (HDCT) and autologous stem-cell transplantation (ASCT) for metastatic germ-cell cancer in Scotland.Patients and Methods
All patients who underwent this treatment between the years 2001 and 2016 at the Beatson West of Scotland Cancer Centre in Glasgow were identified. Information regarding baseline patient and tumor characteristics, prognostic features, HDCT delivery, and survival outcomes were obtained retrospectively from patients’ medical records.Results
Eighteen patients (15 male and 3 female subjects) received HDCT and ASCT in the salvage setting. Of the 14 male patients who had relapsed disease, 8 (57%) were high or very high risk according to the International Prognostic Factor Study Group (IPFSG) risk categorization. The mean time interval between HDCT cycles was 8.6 weeks, which is longer than the specified 3 to 4 weeks in the literature. A total of 67% of patients had no biochemical or radiologic evidence of disease after salvage treatment, including surgery. Progression-free survival and overall survival rates at 2 years were 67% and 72%, respectively. However, 12 patients (67%) and 6 patients (39%) had long-term neurotoxicity and ototoxicity, respectively.Conclusion
Delivery of HDCT and ASCT as salvage treatment for metastatic germ-cell cancer is feasible within a tertiary cancer center with survival outcomes comparable to published literature, although maintaining dose intensity is a challenge. We hope to recruit subjects to the international TIGER trial (ClinicalTrials.gov, NCT02375204), which will attempt to clarify if HDCT is superior to conventional-dose chemotherapy in the salvage setting. 相似文献6.
Caroline Brenner Thomsen Rikke Fredslund Andersen Jan Lindebjerg Torben Frøstrup Hansen Lars Henrik Jensen Anders Jakobsen 《Clinical colorectal cancer》2019,18(1):28-33.e3
Background
RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.Patients and Methods
Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.Results
Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).Conclusion
Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC. 相似文献7.
Aabra Ahmed Ahmed Tahseen Elizabeth England Katrine Wolfe Michael Simhachalam Travis Homan Jenna Sitenga Ryan W. Walters Peter T. Silberstein 《Clinical colorectal cancer》2019,18(1):e1-e7
Background
Colon cancer is the third most frequent cancer diagnosis, and primary payer status has been shown to be associated with treatment modalities and survival in cancer patients. The goal of our study was to determine the between-insurance differences in survival in patients with clinical stage III colon cancer using data from the National Cancer Database (NCDB).Materials and Methods
We identified 130,998 patients with clinical stage III colon cancer in the NCDB diagnosed from 2004 to 2012. Kaplan-Meier curves and multivariable Cox regression models were used to determine the association between insurance status and survival.Results
Patients with private insurance plans were 28%, 30%, and 16% less likely to die than were uninsured patients, Medicaid recipients, and Medicare beneficiaries, respectively. Medicare patients were 14% were less likely to die compared with uninsured patients. Patients receiving chemotherapy were, on average, 65% less likely to die compared with the patients not receiving chemotherapy.Conclusion
Private insurance and a greater socioeconomic status were associated with increased patient survival compared with other insurance plans or the lack of insurance. Future research should continue to unravel how socioeconomic status and insurance status contribute to the quality of care and survival of oncologic patients. 相似文献8.
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9.
Chiara Adriana Pistolese Antonella Castrignanò Francesca Ricci Rosaria Meucci Giusy Croce Mariateresa Mondillo Alberto Collura Tommaso Perretta Roberto Floris 《Clinical breast cancer》2019,19(2):e352-e357
Background
The study aimed to evaluate the feasibility and reliability of ultrasound-guided vacuum-assisted breast biopsy (US-VABB) for sampling of microcalcifications indicative of cancer when stereotactic vacuum-assisted breast biopsy cannot be performed because of reasons such as thin breast tissue, insufficient thickness at compression, and microcalcification situated close to the chest wall or in breast tissue of the axillary tail.Patients and Methods
The study population was selected from among 187 patients with microcalcifications detected on mammogram. The findings were classified using the American College of Radiology criteria as Breast Imaging Reporting and Data System 3, 4, or 5. 30 Thirty were not eligible for stereotactic guidance because of reasons such as small breast size, compression thickness <2 cm, or microcalcification located in the axillary tails or close to chest wall. In 23 patients microcalcifications were detected at ultrasound, and US-VABB was performed. The other 7 patients underwent surgical biopsy. In the 23 patients who underwent US-VABB, multiple core samples were taken after a specimen mammography to ensure that microcalcifications were included.Results
Biopsy was successful in all cases of US-VABB. The procedure was well tolerated, and there were no complications.Conclusion
US-VABB should be preferred over diagnostic surgical biopsy when microcalcifications are sonographically visible and stereotactic guidance is contraindicated. The procedure appears to be reliable and accurate, with added advantages such as low cost and absence of radiation exposure. 相似文献10.
Purpose
To assess the pharmacologic costs of second-line treatments for metastatic renal-cell cancer (mRCC).Methods
The present evaluation was restricted to pivotal phase 3 randomized controlled trials in second-line for mRCC. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival and overall survival (OS) for each trial. The costs of drugs are at the pharmacy of our hospital and are expressed in euros.Results
Our analysis evaluated 5 phase 3 randomized controlled trials including 3112 patients. The lowest cost per month of progression-free survival and OS gained was associated with the use of cabozantinib (€2006 and €1473, respectively), while everolimus had the highest cost per month of OS gained (€28,590).Conclusion
Combining pharmacologic costs of drugs with the measure of efficacy represented by OS, cabozantinib is a cost-effective second-line treatments for patients with mRCC. 相似文献11.
Claudio Vernieri Michele Prisciandaro Monica Milano Maria Silvia Cona Claudia Maggi Marta Brambilla Alessia Mennitto Chiara Fabbroni Elena Farè Sara Cresta Luigi Celio Gabriella Mariani Giulia Bianchi Giuseppe Capri Filippo de Braud 《Clinical breast cancer》2019,19(2):e306-e318
Background
Single-agent gemcitabine is a moderately effective compound in metastatic breast cancer (mBC) treatment. Carboplatin is frequently used in addition to gemcitabine to improve tumor responses, but with an unclear effect on survival outcomes. In this study we evaluated the antitumor efficacy and safety profiles of gemcitabine and carboplatin-gemcitabine in mBC patients.Patients and Methods
We retrospectively collected data on patients treated between April 2012 and February 2018 with gemcitabine 800 mg/m2or carboplatin at an area under the curve of 2 with gemcitabine 800 mg/m2, given on days 1 and 8 every 21 days. We compared progression-free survival (PFS), objective response rate (ORR), overall survival, and incidence of adverse events (AEs) in the 2 cohorts.Results
Of 163 consecutive patients who met the inclusion criteria, 75 received gemcitabine and 88 carboplatin-gemcitabine. Patients in the combination cohort had received a lower number of previous chemotherapy lines (2 vs. 3), and were less likely to have received carboplatin (9 patients [10%] vs. 34 patients [45%]; P < .0001). We found no PFS differences in carboplatin-gemcitabine and gemcitabine cohorts (4.24 vs. 4.61 months; adjusted hazard ratio, 0.98; P = .92), whereas the combination was associated with a trend toward higher ORR (18 patients [20.4%] vs. 8 patients [10.6%]; P = .089) and with significantly higher incidence of Grade 3/4 neutropenia (30 patients [34%] vs. 5 patients [6.6%]; P < .0001).Conclusion
Using carboplatin in addition to gemcitabine is associated with more hematologic AEs but not with better PFS. Although single-agent gemcitabine remains a treatment option for heavily pretreated mBC patients, finding biomarkers of response to platinum salts might help to identify patients more likely to benefit from carboplatin-gemcitabine. 相似文献12.
Chih-An Lin Sung-Liang Yu Hsuan-Yu Chen Huei-Wen Chen Shr-Uen Lin Chia-Ching Chang Chong-Jen Yu Pan-Chyr Yang Chao-Chi Ho 《Journal of thoracic oncology》2019,14(3):513-526
Introduction
Approximately 5% of patients with EGFR-activating mutations acquire EGFR tyrosine kinase inhibitor (TKI) resistance through SCLC transformation. However, the reason for the poor outcome and the molecular basis of EGFR-mutant SCLC that has transformed from adenocarcinoma remain unclear.Methods
In this study, we established two EGFR-mutant SCLC cell lines from lung adenocarcinoma patients after failed EGFR-TKI treatment to investigate their molecular basis and potential therapeutic strategies in the hope of improving patient outcome.Results
These two EGFR-mutant SCLC cell lines displayed two different phenotypes: suspensive and adherent. Both phenotypes shared the same genomic alterations analyzed by array-based comparative genomic hybridization assay. Increased expression of EGFR and mesenchymal markers and decreased expression of neuroendocrine markers were observed in adherent cells. Principal component analysis and hierarchical clustering analysis of RNA microarray revealed that these two cell lines displayed a unique gene expression pattern that was distinctly different from that in NSCLC and classical SCLC cells. Combined treatment using an EGFR-TKI and an AKT inhibitor attenuated cell viabilities in our two cell lines. Moreover, the use of a histone deacetylase inhibitor significantly inhibited the cell viabilities of both cell lines in vitro and in vivo.Conclusion
Our findings suggest that EGFR-mutant SCLC may be a distinct subclass of SCLC that exhibits epithelial-mesenchymal transition phenotypes, and adding an AKT or histone deacetylase inhibitor to pre-existing therapies may be one of the therapeutic choices for transformed EGFR-mutant SCLC. 相似文献13.
Vinicius Ernani Adams Kusi Appiah Alissa Marr Chi Zhang Weining Zhen Lynette M. Smith Apar Kishor Ganti 《Journal of thoracic oncology》2019,14(3):475-481
Introduction
Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting.Methods
Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup.Results
In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1–20.1 months and 18.8–33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7–14.5 mohths and 17.7–21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1–16.8 months and 17.9–20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4–29.4 months and 22.8–26.1 months, respectively; p < .001).Conclusions
SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery. 相似文献14.
Christian Vogel Brigitte Ziegelmüller Börje Ljungberg Karim Bensalah Axel Bex Steven Canfield Rachel H. Giles Milan Hora Markus A. Kuczyk Axel S. Merseburger Thomas Powles Laurence Albiges Fiona Stewart Allseandro Volpe Anno Graser Marcus Schlemmer C. Yuan Thomas Lam Michael Staehler 《Clinical genitourinary cancer》2019,17(2):e345-e355
Objective
To systematically assessed the diagnostic performance of contrast-enhanced computed tomography (CT) compared to other imaging modalities for diagnosing and staging renal-cell carcinoma in adults.Methods
A comprehensive literature search was conducted through various electronic databases. Data from the selected studies were extracted and pooled, and median sensitivity and specificity were calculated wherever possible. Forty studies analyzing data of 4354 patients were included. They examined CT, magnetic resonance imaging (MRI), positron emission tomography–CT, and ultrasound (US).Results
For CT, median sensitivity and specificity were 88% (interquartile range [IQR] 81%-94%) and 75% (IQR 51%-90%), and for MRI they were 87.5% (IQR 75.25%-100%) and 89% (IQR 75%-96%). Staging sensitivity and specificity for CT were 87% and 74.5%, while MRI showed a median sensitivity of 90% and specificity of 75%. For US, the results varied greatly depending on the corresponding technique. Contrast-enhanced US had a median diagnostic sensitivity of 93% (IQR 88.75%-98.25%) combined with mediocre specificity. The diagnostic performance of unenhanced US was poor. For positron emission tomography–CT, diagnostic accuracy values were good but were based on only a small amount of data. Limitations include the strong heterogeneity of data due to the large variety in imaging techniques and tumor histotypes. Contrast-enhanced CT and MRI remain the diagnostic mainstay for renal-cell carcinoma, with almost equally high diagnostic and staging accuracy.Conclusion
For specific questions, a combination of different imaging techniques such as CT or MRI and contrast-enhanced US may be useful. There is a need for future large prospective studies to further increase the quality of evidence. 相似文献15.
Hannah O’Farrell Bryant Harbourne Zimple Kurlawala Yusuke Inoue Amy L. Nagelberg Victor D. Martinez Daniel Lu Min Hee Oh Bradley P. Coe Kelsie L. Thu Romel Somwar Stephen Lam Wan L. Lam Arun M. Unni Levi Beverly William W. Lockwood 《Journal of thoracic oncology》2019,14(4):656-671
Introduction
Targeted therapies for lung adenocarcinoma (LUAD) have improved patient outcomes; however, drug resistance remains a major problem. One strategy to achieve durable response is to develop combination-based therapies that target both mutated oncogenes and key modifiers of oncogene-driven tumorigenesis. This is based on the premise that mutated oncogenes, although necessary, are not sufficient for malignant transformation. We aimed to uncover genetic alterations that cooperate with mutant EGFR during LUAD development.Methods
We performed integrative genomic analyses, combining copy number, gene expression and mutational information for over 500 LUAD tumors. Co-immunoprecipitation and Western blot analysis were performed in LUAD cell lines to confirm candidate interactions while RNA interference and gene overexpression were used for in vitro and in vivo functional assessment.Results
We identified frequent amplifications/deletions of chromosomal regions affecting the activity of genes specifically in the context of EGFR mutation, including amplification of the mutant EGFR allele and deletion of dual specificity phosphatase 4 (DUSP4), which have both previously been reported. In addition, we identified the novel amplification of a segment of chromosome arm 16p in mutant-EGFR tumors corresponding to increased expression of Golgi Associated, Gamma Adaptin Ear Containing, ARF Binding Protein 2 (GGA2), which functions in protein trafficking and sorting. We found that GGA2 interacts with EGFR, increases EGFR protein levels and modifies EGFR degradation after ligand stimulation. Furthermore, we show that overexpression of GGA2 enhances EGFR mediated transformation while GGA2 knockdown reduces the colony and tumor forming ability of EGFR mutant LUAD.Conclusions
These data suggest that overexpression of GGA2 in LUAD tumors results in the accumulation of EGFR protein and increased EGFR signaling, which helps drive tumor progression. Thus, GGA2 plays a cooperative role with EGFR during LUAD development and is a potential therapeutic target for combination-based strategies in LUAD. 相似文献16.
Martin Reck Leora Horn Silvia Novello Fabrice Barlesi István Albert Erzsébet Juhász Dariusz Kowalski Gilles Robinet Jacques Cadranel Paolo Bidoli John Chung Arno Fritsch Uta Drews Andrea Wagner Ramaswamy Govindan 《Journal of thoracic oncology》2019,14(4):701-711
Introduction
This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.Methods
In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days–on, 4 days–off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.Results
A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2–5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6–5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820–1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9–11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7–11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776–1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).Conclusions
Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated. 相似文献17.
Dangui Chen Di Zhou Jingyan Xu Rongfu Zhou Jian Ouyang Bing Chen 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):e159-e164
Background
Multiple myeloma (MM) is a heterogeneous disease characterized by chromosomal translocation, deletion, and amplification in plasma cells, resulting in a huge heterogeneity in its outcomes. In the era of novel agents such as bortezomib, thalidomide, and the cycles of treatment, risk stratification by chromosomal aberrations may enable a more rational risk-stratification selection of therapeutic approaches in patients with MM.Patients and Methods
We performed a retrospective study in 63 patients with MM; 29 (46.03%) with 1q21 gain and 34 (53.97%) without gain.Result
In all patients, we did not find that the patients with 1q21 gain had significantly better survival compared with patients without 1q21 gain (overall survival, P = .6916; progression-free survival, P = .8740). However, in 1q21 gain patients, we found that the bortezomib group had significantly better survival compared with the non-bortezomib group in terms of both the 3-year estimated overall survival (82.3% vs. 18.8%; P = .0154) and progression-free survival (62.8% vs. 8.75%; P = .0385).Conclusion
1q21 gain detected by fluorescence in situ hybridization is not as high risk for poor prognosis with regard to time for overall survival. And the clinical outcome of patients with 1q21 gain can be improved in those who received no less than 4 cycles of bortezomib-based therapy (bortezomib, thalidomide, and dexamethasone). 相似文献18.
M.R. Ferreira K. Thomas L. Truelove A. Khan C. Parker D.P. Dearnaley S. Gulliford 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(6):374-384
Aims
Pelvic lymph node (PLN) radiotherapy for high-risk prostate cancer is limited by late gastrointestinal toxicity. Application of rectal and bowel constraints may reduce risks of side-effects. We evaluated associations between intensity-modulated radiotherapy (IMRT) dose-volume data and long-term gastrointestinal toxicity.Materials and methods
Data from a single-centre dose-escalation trial of PLN-IMRT were analysed, including conventionally fractionated (CFRT) and hypofractionated (HFRT) radiotherapy schedules. Associations between volumes of rectum and bowel receiving specified doses and clinician- and patient-reported toxicity outcomes were investigated independently. A metric, δ median (δM), was defined as the difference in the medians of a volume between groups with and without toxicity at a specified dose and was used to test for statistically significant differences.Results
Constraints were respected in most patients and, when exceeded, led to higher rates of gastrointestinal toxicity. Biologically relevant associations between rectum dose-points and toxicity were more numerous with both mild and moderate toxicity thresholds, but statistical significance was limited after correction for false discovery rate. Rectal V50Gy (CFRT) associated with grade 2+ bleeding; bowel V43Gy and V47 (HFRT/4 days/week schedule) associated with patient-reported loose stools and diarrhoea, respectively. Further investigation showed that CFRT patients with rectal bleeding had a mean rectal V50Gy above the treatment planning constraint.Conclusions
When dose-volume parameters are kept below tight constraints, toxicity is low. Residual dosimetry loses much of its predictive power for gastrointestinal toxicity in the setting of PLN-IMRT for prostate cancer. We have benchmarked dose-volume constraints for safely delivering PLN-IMRT using CFRT or HFRT. 相似文献19.
Rafiye Ciftciler Haluk Demiroglu Yahya Buyukasık Elifcan Aladag Salih Aksu Ibrahim C. Haznedaroglu Nilgun Sayınalp Osman Ozcebe Umit Yavuz Malkan Hakan Goker 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):177-182
Background
Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.Patients and Methods
We retrospectively analyzed the clinical outcome of 91 patients who were diagnosed with treatment-refractory AML at Hacettepe University Hospital between January 2002 and June 2018. Patients' disease status included refractory AML, defined as failure to respond to standard induction chemotherapy and relapse within 6 months after first complete remission.Results
The median follow-up was 12 months (range, 0.5-184 months) for the entire group. Kaplan-Meier estimates of the 3-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 67% and 12%, respectively. Additionally, the Kaplan-Meier estimates of 5-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 44% and 4%, respectively (P < .001). Complete remission was obtained in 25 patients (83.3%) who underwent allo-HSCT; however, the disease of only 3 patients (3.8%) exhibited complete response after salvage chemotherapy.Conclusion
Allo-HSCT is still the best-known treatment option with curative potential in patients with treatment-refractory AML. Therefore, all efforts should be made in an attempt to find a suitable matched donor in order to perform allo-HSCT. 相似文献20.
Tarek M.K. Motawi Nadia I. Zakhary Hebatallah A. Darwish Hassan M. Abdalla Samer A. Tadros 《Clinical breast cancer》2019,19(2):e276-e282