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1.
Nikola S. Mutschler Christoph Scholz Thomas W.P. Friedl Thomas Zwingers Peter A. Fasching Matthias W. Beckmann Tanja Fehm Svjetlana Mohrmann Jessica Salmen Carola Ziegler Bernadette Jäger Peter Widschwendter Nikolaus de Gregorio Fabienne Schochter Sven Mahner Nadia Harbeck Tobias Weissenbacher Julia Jückstock Brigitte Rack 《Clinical breast cancer》2018,18(2):175-183
Background
In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial.Patients and Methods
The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node–positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (≥ 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses.Results
Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by ≥ 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067).Conclusion
Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS. 相似文献2.
C.M. Booth S. Nanji X. Wei Y. Peng J.J. Biagi T.P. Hanna M.K. Krzyzanowska W.J. Mackillop 《Clinical oncology (Royal College of Radiologists (Great Britain))》2017,29(1):e29-e38
Aims
Although guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer, many state that ACT may be considered in high-risk disease. Here we describe practice patterns and outcomes associated with ACT in the general population.Materials and methods
All cases of colon cancer diagnosed in Ontario 2002–2008 were identified using the Ontario Cancer Registry, which was linked to electronic treatment records. Pathology reports were obtained for a 25% random sample of cases. High-risk disease was defined as: T4 tumours, <12 lymph nodes, poorly differentiated histology, lymphovascular invasion. Modified Poisson regression was used to evaluate factors associated with ACT. The Cox proportional hazards model was used to explore the association between ACT and cancer-specific (CSS) and overall survival.Results
The study population included 2488 patients with stage II colon cancer; 1175 (47%) with high-risk disease. ACT was delivered to 18% of all patients and 24% of patients with high-risk disease. ACT rates were higher among younger patients (51% age 20–49 years versus 16% age 70–79, P < 0.001) and varied considerably across geographic regions (range 10–39%, P < 0.001). Among all patients with stage II colon cancer, ACT was not associated with improved CSS (hazard ratio 1.41, 95% confidence interval 1.09–1.82) or overall survival (hazard ratio 1.16, 95% confidence interval 0.94–1.42). Stratified survival analysis for patients with high-risk disease did not show benefit to ACT (CSS hazard ratio 1.14, 95% confidence interval 0.84–1.55; overall survival hazard ratio 1.02, 95% confidence interval 0.79–1.31).Conclusion
ACT use varies across age groups and geographic regions. ACT is not associated with improved survival among patients with stage II colon cancer including those with high-risk disease. 相似文献3.
Sharon F. McGee Tinghua Zhang Hannah Jonker Scott A. Laurie Glen Goss Garth Nicholas Khalid Albaimani Paul Wheatley-Price 《Clinical lung cancer》2018,19(1):e91-e99
Background
Palliative systemic therapy is frequently underutilized in patients with advanced non–small-cell lung cancer (NSCLC), for many reasons. The aim of this study was to identify patient-reported factors that may predict for treatment decisions and survival in advanced NSCLC, using the Edmonton Symptom Assessment Scale (ESAS), which is a self-reported questionnaire that quantifies symptom burden by asking patients to rate the severity of 9 common symptoms.Patients and Methods
With ethics approval, we analyzed ESAS scores at initial oncology consultation for 461 patients with advanced NSCLC seen at The Ottawa Hospital Cancer Centre from 2009 to 2012. Subgroup analysis was performed to determine if treatment strategies or overall survival (OS) were related to the total symptom burden, as defined by the sum of the individual ESAS symptom scores.Results
The severity of the ESAS total symptom burden score was positively correlated with Eastern Cooperative Oncology Group performance status (R = 0.48; P < .0001). Furthermore, patients with a higher symptom burden were less likely to receive systemic chemotherapy than those with fewer symptoms (43% vs. 66%; P < .0001), and had a significantly reduced OS (5.5 vs. 9.9 months; P < .0001). A higher ESAS symptom burden score was also associated with reduced OS by univariate analysis (hazard ratio, 1.78; 95% confidence interval, 1.45-2.18; P < .0001), although multivariate analysis showed only a trend towards significance (hazard ratio, 1.27; 95% confidence interval, 0.99-1.62; P = .06).Conclusions
Overall, this demonstrates a novel role for the ESAS as a prognostic tool that could complement existing patient assessment models, such as Eastern Cooperative Oncology Group performance status, in the development of optimal treatment plans and estimation of survival, in patients with advanced lung cancer. 相似文献4.
Ye Zheng Anhui Shi Weihu Wang Huiming Yu Rong Yu Dongming Li Bo Xu Huimin Ma Jing You Dan Zhao Leilei Jiang Jianhao Geng Guangying Zhu 《Clinical lung cancer》2018,19(4):e399-e404
Purpose
Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non–small-cell lung cancer (NSCLC) patients treated with SABR.Patients and Methods
Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression-free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan-Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model.Results
At a median follow-up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05-1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16-3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8+ T-cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01-1.28; P = .01).Conclusion
A higher posttreatment cytotoxic CD8+ T-cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen-specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients. 相似文献5.
Oliver Gautschi Sacha I. Rothschild Qiyu Li Klazien Matter-Walstra Alfred Zippelius Daniel C. Betticher Martin Früh Rolf A. Stahel Richard Cathomas Daniel Rauch Miklos Pless Solange Peters Patrizia Froesch Thilo Zander Martina Schneider Christine Biaggi Nicolas Mach Adrian F. Ochsenbein 《Clinical lung cancer》2017,18(3):303-309
Background
Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non–small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.Patients and Methods
We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared.Results
The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1.Conclusion
The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs. 相似文献6.
Nobuaki Matsubara Yoko Yamada Ken-ichi Tabata Takefumi Satoh Naoto Kamiya Hiroyoshi Suzuki Takashi Kawahara Hiroji Uemura Akihiro Yano Satoru Kawakami Masafumi Otsuka Satoshi Fukasawa 《Clinical genitourinary cancer》2018,16(2):142-148
Background
Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined.Patients and Methods
We retrospectively reviewed the records of chemotherapy-naive patients with metastatic castration-resistant prostate cancer who had received sequential treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA). Prostate-specific antigen (PSA) response rates (defined as ≥ 50% PSA decline from baseline), first-line progression-free survival (PFS), second-line PFS, combined PFS (defined as first-line PFS plus second-line PFS), and overall survival are compared between the 2 sequence groups.Results
A total of 97 patients received sequential treatment with AA and ENZA; 50 patients were in the AA-ENZA group, and 47 patients were in the ENZA-AA group. The PSA response rate to first-line treatment was not significantly different between AA (48%) and ENZA (51%) (P = .840). However, a significant difference was observed in the PSA response rate to second-line treatment (AA, 6.4% vs. ENZA, 30%; P = .004). The median combined PFS was not significantly different between sequence groups (hazard ratio, 0.71; 95% confidence interval, 0.46-1.08; log-rank P = .105). The order of addition also had no significant effect on median overall survival (hazard ratio, 0.98; 95% confidence interval, 0.64-1.52; log-rank P = .834).Conclusion
With the exception of the second-line PSA response, there was no significant difference in clinical outcomes between the AA-ENZA and ENZA-AA groups. Our results might be useful reference in daily practice, especially for patients who do not have a suitable general condition for chemotherapy. 相似文献7.
Tomoyuki Abe Hironobu Amano Tsuyoshi Kobayashi Keiji Hanada Masahiro Nakahara Hideki Ohdan Toshio Noriyuki 《European journal of surgical oncology》2018,44(10):1573-1579
Background
The neutrophil-to-lymphocyte ratio (NLR), which reflects the cancer-induced systemic inflammation response, has been proposed as a risk factor for poor long-term prognosis in cancer. We investigated the prognostic role of the NLR and the relationship between the NLR and TNM stage in pancreatic ductal adenocarcinoma (PDAC) patients following curative resection.Methods
One-hundred thirty-eight consecutive patients with resected PDAC were enrolled between 2004 and 2014. Univariate and multivariate analyses identified variables associated with overall survival (OS) and recurrence-free survival (RFS). Patients were stratified according to the NLR, with an NLR cut-off value of 2.2 being estimated by receiver operating characteristic curve.Results
Compared to patients with a low NLR (≤2.2), those with a high preoperative NLR (>2.2) had worse OS and RFS (P = 0.017, P = 0.029, respectively). For early-stage tumors, tumor size ≥20 mm and a high NLR were independent risk factors for poor OS (hazard ratio (HR): 3.255, 95% confidence interval (CI): 1.082–9.789, P = 0.036; HR: 3.690, 95% CI: 1.026–13.272, P = 0.046, respectively) and RFS (HR: 3.575, 95% CI: 1.174–10.892, P = 0.025; HR: 5.380, 95% CI: 1.587–18.234, P = 0.007, respectively). The NLR was not correlated with prognosis in patients with advanced stages.Conclusions
An elevated preoperative NLR was an important prognosticator for early TNM stage PDAC. The NLR, which is calculated using inexpensive and readily available biomarkers, could be a novel tool for predicting long-term survival in patients, especially those with early stage PDAC. 相似文献8.
Lubomir Bodnar Rafał Stec Szczepan Cierniak Agnieszka Synowiec Gabriel Wcisło Marzena Jesiotr Robert Koktysz Paweł Chrom Cezary Szczylik 《Clinical genitourinary cancer》2018,16(4):257-265
Background
The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway.Patients and Methods
In a prospective, single-arm, phase II study, patients with mRCC received everolimus (10 mg/d) in a 30-day cycle. We performed a prospectively planned evaluation of the potential biomarkers of the WNT/β-catenin pathway.Results
The serum level of soluble E-cadherin (sE-cadherin) in patients with RCC was significantly greater than that in the controls (71.62 ± 22.28 pg/mL vs. 54.26 ± 10.317 pg/mL; P = .0069). After 2 cycles of everolimus therapy, we observed a significance increase in sE-cadherin (from 71.81 ± 21.18 pg/mL to 77.50 ± 28.212 pg/mL; P = .0151). The Dickkopf-1 protein levels in the study and control groups were not significantly different (P = .2135). The favorable independent predictors for everolimus therapy were normal lactate dehydrogenase level before treatment (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28-0.98; P = .0443) and low sE-cadherin level (HR, 0.54; 95% CI, 0.29-0.98; P = .0422). On multivariate analysis, we observed that worse overall survival was seen in patients with a lower regression coefficient of sE-cadherin after 2 cycles of treatment (HR, 2.60; 95% CI, 1.23-5.52; P = .0128), an increased corrected calcium level (HR, 3.09; 95% CI, 1.21-7.88; P = .0180), and an increased lactate dehydrogenase level before treatment (HR, 1.98; 95% CI, 1.02-3.83; P = .0426).Conclusion
WNT/β-catenin component expression in patients with mRCC had no effect on progression-free survival or overall survival. However, we found that the sE-cadherin level might interact with response to everolimus therapy, although confirmation in future studies is needed. 相似文献9.
Leonardo S. Lino-Silva Reynaldo Loaeza-Belmont Miguel A. Gómez Álvarez Itzel Vela-Sarmiento José M. Aguilar-Romero Jorge A. Domínguez-Rodríguez Rosa A. Salcedo-Hernández Erika B. Ruiz-García Héctor A. Maldonado-Martínez Ángel Herrera-Gómez 《Clinical colorectal cancer》2017,16(1):73-77
Background
Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane.Materials and Methods
We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed.Results
The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033).Conclusion
MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival. 相似文献10.
Anna Buder Maximilian J. Hochmair Sophia Schwab Tatjana Bundalo Peter Schenk Peter Errhalt Romana E. Mikes Gudrun Absenger Kurt Patocka Bernhard Baumgartner Ulrike Setinek Otto C. Burghuber Helmut Prosch Robert Pirker Martin Filipits 《Journal of thoracic oncology》2018,13(6):821-830
Introduction
Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non–small-cell lung cancer who have been pre-treated with EGFR–tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.Methods
From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non–small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients.Results
T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1–12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92–3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89–5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers.Conclusion
Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib. 相似文献11.
Antoine Thiery-Vuillemin Tiphaine Cholley Fabien Calcagno Marion Hugues Tristan Maurina Samuel Limat Thierry Nguyen Tan Hon Hamadi Almotlak Guillaume Mouillet Virginie Nerich 《Clinical genitourinary cancer》2018,16(2):e297-e305
Purpose
To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies.Patients and Methods
Two hundred twenty-four consecutive patients with histologically confirmed mccRCC who received targeted therapy on first-line treatment between January 2007 and March 2015 were included. The primary end point was OS for metastatic first-line or second-line treatment. An analysis of prognostic factors of long survival was performed using a 2-step approach: univariate, then multivariate analysis.Results
Median OS [95% confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were identified in first-line treatment: Memorial Sloan Kettering Cancer Center (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval] = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10?4), metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95% confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different prognostic factors predicted long survival: toxicity for first-line treatment discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10?4), duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10?4), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936 [0.607-1.443], respectively, P = .02).Conclusion
These real-life data confirm the positive impact of targeted therapy in the mccRCC setting. Moreover, it emphasizes the importance of considering many factors in order to better estimate prognosis in patient pretreated with systemic therapy. 相似文献12.
Raffaele Ratta Elena Verzoni Massimo Di Maio Paolo Grassi Maurizio Colecchia Giovanni Fucà Filippo de Braud Giuseppe Procopio 《Clinical genitourinary cancer》2018,16(4):e735-e742
Background
The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).Patients and Methods
The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed.Results
A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001).Conclusion
Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes. 相似文献13.
Sigurd M. Hald Mehrdad Rakaee Inigo Martinez Elin Richardsen Samer Al-Saad Erna-Elise Paulsen Egil Støre Blix Thomas Kilvaer Sigve Andersen Lill-Tove Busund Roy M. Bremnes Tom Donnem 《Clinical lung cancer》2018,19(3):249-259.e2
Background
Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non–small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3+ tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification.Materials and Methods
Primary tumor tissue from 553 stage I-IIIB NSCLC patients and 143 corresponding metastatic lymph nodes were collected. The expression of LAG-3 was evaluated by immunohistochemistry on tissue microarrays.Results
On univariate analysis, LAG-3+ TILs in the intraepithelial and stromal compartments of primary tumors and in the intraepithelial and extraepithelial compartments of metastatic lymph nodes were associated with improved disease-specific survival (DSS). On multivariate analysis, stromal LAG-3+ TILs were a significant independent predictor of improved DSS (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.43-0.82; P = .002). Stromal LAG-3+ TILs did not have prognostic impact across all pathologic stages. In the metastatic lymph nodes, intraepithelial (HR, 0.61; 95% CI, 0.38-0.99; P = .049) and extraepithelial (HR, 0.54; 95% CI, 0.29-0.70; P < .001) LAG-3+ TILs were independently associated with favorable DSS.Conclusion
LAG-3+ TILs are an independent positive prognostic factor in stage I-IIIB NSCLC. LAG-3 in metastatic lymph nodes is a candidate marker for an immunoscore in NSCLC. 相似文献14.
Eman Z. Kandeel Ghada El Sayed Nahla Elsharkawy Dalia Negm Eldin Hanan R. Nassar Dalia Ibrahiem Randa Amin Marwa Hanafi Mohamed Khalil Azza Kamel 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(8):541-547
Background
The significance of FMS-like tyrosine kinase 3 (FLT3)-ITD mutation in acute myeloid leukemia (AML) prognosis has been well established. The aims of this study were to investigate the prognostic impact of the FLT3 protein (CD135) expression and its association with FLT3-ITD mutation, and to identify its role in minimal residual disease.Patients and Methods
CD135 was measured by flow cytometry on leukemic blasts of 257 adults with de novo AML. High expression of CD135 ≥ 20% was correlated with clinical, laboratory, and other prognostic factors that influenced treatment outcome. FLT3-ITD mutation was tested by PCR.Results
The frequency of CD135 expression was 138 (53.7%) of 257. FLT3-ITD was detected in (21.4%). Positive CD135 expression was associated with high total leukocyte count (P = .006), platelet count (P = .003), monocytic leukemia (P < .001), and CD34 (P = .008) and CD117 (P = .006) expression. CD135 expression ≥ 25% was a predictor of FLT3-ITD mutation (P = .03). CD135 overexpression was a negative predictor of complete remission and of postinduction minimal residual disease at days 14 and 28 (P < .001). CD135 had an adverse impact on overall and disease-free survival (68.5% vs. 15%, P = .002). Multivariate analysis indicated CD135 was the sole independent prognostic factor for overall survival (hazard ratio = 2.49; 95% confidence interval, 1.855-3.345; P < .001).Conclusion
CD135 is emerging as a prognostic factor, a new marker for minimal residual disease, and a potential novel therapeutic target of AML. 相似文献15.
Yunfu Deng Guangzhi Ma Wen Li Ting Wang Yaqin Zhao Qiang Wu 《Clinical breast cancer》2018,18(5):e943-e953
Background
This meta-analysis of randomized controlled trials aimed to comprehensively assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in advanced breast cancer (ABC) with hormone-receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2?) disease.Methods
We performed a systematical search using Cochrane Library, PubMed, Embase, and Web of Science up to March 2018. Only phase 2 and 3 randomized clinical trials assessing the efficacy and toxicity of the combination regimen of CDK4/6 inhibitors plus hormone therapy compared with hormone therapy alone were eligible for this meta-analysis. The pooled analyses of relative risk (RR) and hazard ratio were carried out by Stata software.Results
A total of 7 randomized controlled trials including 3854 patients with HR+/HER2? ABC were included in this meta-analysis. The pooled hazard ratio for progression-free survival was 0.54 (95% confidence interval, 0.49-0.59; P < .001), and the pooled RR for the objective response rate in all intent-to-treat patients was 1.51 (95% confidence interval, 1.26-1.81; P < .001). The pooled RRs for all grade adverse events (AEs) and grade 3/4 AEs were 1.07 (95% confidence interval, 1.03-1.11; P < .001) and 2.81 (95% confidence interval, 2.54-3.11; P < .001), respectively. However, to investigate the influence of CDK4/6 inhibitors on overall survival, sufficient follow-up is still needed.Conclusion
CDK4/6 inhibitors plus hormone therapy can significantly prolong the progression-free survival of patients with HR+/HER2? ABC and improve the objective response rate compared to conventional hormone therapy alone. The combined regimen results in a higher risk of AEs, especially grade 3/4 AEs. 相似文献16.
Yu Jin Lim Ji Hyun Chang Hak-Jae Kim Bhumsuk Keam Tae Min Kim Dong-Wan Kim Jin Chul Paeng Keon Wook Kang June-Key Chung Yoon Kyung Jeon Doo Hyun Chung Hong-Gyun Wu 《Clinical lung cancer》2017,18(3):e169-e178
Background
Although previous in vitro data have suggested a more radio-sensitive nature of epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC) cell lines, the clinical behavior according to the EGFR mutational status has not been well-established. In this study, we performed a comparative outcome analysis of EGFR-mutant and wild-type locally advanced NSCLC with chemoradiotherapy (CRT).Patients and Methods
A total of 102 patients with stage III nonsquamous NSCLC undergoing primary CRT were identified. Clinicopathologic characteristics, including the degree of glucose uptake, were evaluated. Failure patterns considering the radiation field and survival outcomes were compared according to the EGFR mutational status.Results
Pre- and post-CRT maximum standardized uptake values were significantly lower in EGFR-mutant tumors (P = .010 and .018, respectively). The overall response rate was higher in the EGFR-mutant group compared with the wild-type (89% vs. 64%, respectively; P = .023). The 3-year overall survival rate was better with the genetic alteration (68.0% vs. 47.4%, P = .046), but the statistical significance did not remain in multivariate analysis (hazard ratio, 0.68; 95% confidence interval, 0.30-1.55). Considering the tumor progression inside or outside the radiation field, the EGFR-mutant group showed longer in-field time to progression (P = .002), even after adjusting for other related baseline variables (hazard ratio, 0.27; 95% confidence interval, 0.11-0.71).Conclusion
The differential metabolic activity, failure patterns, and prognosis suggest the distinct nature of the EGFR-mutant tumors. EGFR mutational status needs to be considered for more precise curative-intent treatment strategies of locally advanced nonsquamous NSCLC. 相似文献17.
Andrea Mari Mohammad Abufaraj Beat Foerster Mehmet ?zsoy Alberto Briganti Morgan Rouprêt Pierre I. Karakiewicz Romain Mathieu David D&#x;Andrea Daher C. Chade Shahrokh F. Shariat 《Clinical genitourinary cancer》2018,16(3):e619-e627
Introduction
The purpose of the present study was to investigate the association of smoking with biochemical recurrence (BCR) and metastasis in radiation-recurrent prostate cancer (PCa) patients undergoing salvage radical prostatectomy (SRP).Patients and Methods
A total of 214 patients treated with SRP for radiation-recurrent PCa in 5 tertiary referral centers were included from January 2007 to December 2015. Kaplan-Meier analyses were used to assess the time to BCR and metastasis. Pre- and postoperative multivariable Cox proportional hazard regression models were fitted.Results
Overall, 120 (56.1%), 49 (22.9%), and 45 (21%) patients were never, former, and current smokers, respectively. Low-, medium-, and high-cumulative smoking exposure was registered in 59.8%, 16.4%, and 23.8% of cases, respectively. Patients with high cumulative smoking exposure had a significantly greater rate of a pathologic Gleason score of ≥ 8 (P = .01) and extracapsular extension (P = .004). Smoking status, cumulative smoking exposure, intensity, and duration were significantly associated with BCR-free survival (P < .001 for all). Smoking status, cumulative smoking exposure, and smoking intensity were significantly associated with metastasis-free survival (P = .03 for all). High cumulative smoking exposure was independently associated with BCR in both pre- (hazard ratio, 2.23; P = .001) and postoperative (hazard ratio, 1.64; P = .04) multivariable models adjusted for the effects of established clinicopathologic features. Smoking cessation did not affect either BCR- or metastasis-free survival (P = .56 and P = .40, respectively).Conclusion
High cumulative smoking exposure was associated with the biologic and clinical aggressiveness of PCa in patients treated with SRP for radiation-recurrent disease. Smoking is a modifiable risk factor that detrimentally affected the outcomes, even in patients with advanced PCa. 相似文献18.
M.L. Yap M. Tieu J. Sappiatzer T. Panzarella J. Cuartero D. McCready A. Fyles 《Clinical oncology (Royal College of Radiologists (Great Britain))》2018,30(7):427-432
Aims
The use of bolus in post-mastectomy radiotherapy (PMRT) varies significantly between institutions. We report on chest wall recurrence and acute toxicity rates for PMRT patients treated with selective use of bolus.Materials and methods
We analysed PMRT patients who received adjuvant chest wall radiotherapy for invasive breast cancer between 2004 and 2009. Patient, tumour and cancer outcomes were collected from a prospective database, with additional radiotherapy and acute toxicity details supplemented retrospectively. Chest wall bolus was reserved for patients considered at high risk of local recurrence.Results
There were 314 patients suitable for analysis: 52 received bolus, 262 did not. The mean age was 53.2 years. The median follow-up was 4.2 years. The most common T stage was T2 (37%), followed by T3/T4 (33%). There were 229 patients (73%) who had N+ disease; 213 (68%) patients had grade 3 cancer. Oestrogen receptor was positive in 176 (56%) cases, progesterone receptor was positive in 134 (43%) and HER2 receptor was positive in 24 (8%). Lymphovascular space invasion was present in 146 patients (46%), dermal invasion in 30 patients (10%) and positive margin in 14 patients (4%). The 4 year chest wall recurrence rate was 14% (95% confidence interval 5.4–26.8%) in the bolus group and only 3.5% (95% confidence interval 1.6–6.4%) in the non-bolus group. On univariate analysis, use of bolus was associated with a significant difference in chest wall recurrence (hazard ratio 3.09; 1.15–8.33; P = 0.025). However, when taking into account margin status, this significance was lost (hazard ratio = 2.45; 95% confidence interval 0.80–7.50, P = 0.12). There was a higher rate of acute grade 2 skin toxicity in patients receiving bolus compared with those without, 40% versus 21% (P = 0.01).Conclusions
The selective use of bolus resulted in a small risk of chest wall recurrence rates for low-risk patients. This suggests that the routine use of bolus in PMRT patients may be unnecessary. 相似文献19.
Sonam Sharma Matthew T. McMillan Abigail Doucette Roger B. Cohen Abigail Berman William Levin Charles B. Simone Jacob Shabason 《Clinical lung cancer》2018,19(3):260-269.e3
Introduction
Patients with small-cell lung cancer (SCLC) have a high incidence of occult brain metastases and are often treated with prophylactic cranial irradiation (PCI). Despite a small survival advantage in some studies, the role of PCI in extensive stage SCLC remains controversial. We used the National Cancer Database to assess survival of patients with metastatic SCLC treated with PCI.Patients and Methods
Metastatic SCLC patients without brain metastases were identified. To minimize treatment selection bias, patients with an overall survival (OS) < 6 months were excluded. Cox regression identified variables associated with OS. Patients were propensity score-matched on factors associated with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan–Meier estimates.Results
In the overall cohort (n = 4257), treatment with PCI (n = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence interval, 0.60-0.74; P < .0001). Comparisons of propensity score-matched cohorts revealed a significant survival benefit for patients who received PCI in median OS (13.9 vs. 11.1 months; P < .0001), as well as 1- and 2-year OS (61.2% vs. 44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit persisted even after excluding patients who survived < 9 months (median: 15.3 vs. 12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI were Caucasian race, younger age, and lower Charlson–Deyo score.Conclusion
Using a modern population-based data set, we showed that metastatic SCLC patients treated with PCI have significantly improved OS. This large retrospective study helps address the conflicting prospective data. 相似文献20.
P. Zhang C.-Z. Li C.-T. Wu G.-M. Jiao F. Yan H.-C. Zhu X.-P. Zhang 《European journal of surgical oncology》2017,43(2):285-293