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1.
Charles J. Ryan Thian Kheoh Jinhui Li Arturo Molina Peter De Porre Joan Carles Eleni Efstathiou Philip W. Kantoff Peter F.A. Mulders Fred Saad Kim N. Chi 《Clinical genitourinary cancer》2018,16(1):72-77.e1
Background
Radiographic progression-free survival (rPFS) is associated with overall survival (OS) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Using readily assessable baseline clinical and laboratory parameters, we developed a prognostic index model for rPFS in chemotherapy-naïve mCRPC patients without visceral disease who were treated with abiraterone acetate plus prednisone.Methods
Data from the abiraterone acetate plus prednisone arm of COU-AA-302 were used. rPFS was defined based on modified Prostate Cancer Working Group 2 criteria. Baseline variables were assessed for association with rPFS through univariate Cox modeling. The lower (LLN) and upper (ULN) limits of laboratory normal were used to dichotomize most laboratory parameters; baseline median was used to dichotomize prostate-specific antigen (PSA). Prognostic factors for rPFS were identified by multivariate Cox modeling. Model accuracy was estimated by the C-index.Results
Presence of lymph node metastasis (hazard ratio [HR] = 1.76, P < .0001), lactate dehydrogenase > ULN (234 IU/L) (HR = 1.71, P = .0001), ≥ 10 bone metastases (HR = 1.71, P = .0015), hemoglobin ≤ LLN (12.7 g/dL) (HR = 1.47, P = .0030) and PSA > 39.5 ng/mL (HR = 1.42, P = .0078) were associated with poor outcome. Patients were categorized into 3 prognostic groups (good, n = 230; intermediate, n = 152; poor, n = 164) based on number of risk factors. Median rPFS was calculated (27.6, 16.6, and 8.3 months for good, intermediate, and poor, respectively). The C-index was 0.83 (95% confidence interval = 0.73-0.91).Conclusions
The prognostic index model for rPFS reveals differential outcomes based on factors readily available in clinical practice. If validated, this model can be integrated into clinical practice and design of risk-stratified trials. 相似文献2.
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3.
4.
Bonnie Glisson Benjamin Besse Manuel Cobo Dols Sarita Dubey Marco Schupp Rajul Jain Yizhou Jiang Hari Menon Kristiaan Nackaerts Sergey Orlov Luis Paz-Ares Rodryg Ramlau Rui Tang Yilong Zhang Min Zhu 《Clinical lung cancer》2017,18(6):615-625.e8
Introduction/Background
In this randomized, double-blind, placebo-controlled phase 1b/2 study we assessed the efficacy/safety of rilotumumab or ganitumab combined with etoposide and carboplatin or cisplatin as first-line treatment in patients with extensive stage small-cell lung cancer (ES-SCLC).Patients and Methods
In the phase 1b study, patients received rilotumumab 15 mg/kg or ganitumab 18 mg/kg with etoposide and carboplatin or cisplatin. In the phase 2 study, patients were randomly assigned 1:1:1 to receive placebo, rilotumumab, or ganitumab with etoposide and carboplatin or cisplatin. Chemotherapy was administered for ≤ 6 cycles; rilotumumab, ganitumab, or placebo was then continued as maintenance therapy. The primary end points were incidence of dose-limiting toxicities (DLTs; phase 1b) and overall survival (OS; phase 2). Secondary end points included progression-free survival (PFS) and safety.Results
In the phase 1b study (n = 28), 1 patient treated with ganitumab experienced a DLT (Grade 4 neutropenia/thrombocytopenia lasting ≥ 7 days). In the phase 2 study, 185 patients were enrolled (placebo, n = 61; rilotumumab, n = 62; ganitumab, n = 62). Median OS was 10.8, 12.2 (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.56-1.25; P = .384), and 10.7 (HR, 0.95; 95% CI, 0.63-1.41; P = .787) months, in placebo, rilotumumab, or ganitumumab arms, respectively. Median PFS was 5.4, 5.4 (HR, 1.05; 95% CI, 0.71-1.54; P = .797), and 5.5 (HR, 1.05; 95% CI, 0.72-1.55; P = .780) months, respectively. Adverse events resulting in treatment discontinuation occurred in 11 (19%), 10 (16%), and 7 (12%) patients, respectively. Serum biomarker analysis showed improved survival for patients with baseline hepatocyte growth factor levels below the median in the rilotumumab arm.Conclusion
Although the combination of rilotumumab or ganitumab with chemotherapy was tolerable, overall outcomes were not improved in patients with ES-SCLC. 相似文献5.
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6.
Daniel Glick Stephen Lyen Sonja Kandel Shane Shapera Lisa W. Le Patricia Lindsay Olive Wong Andrea Bezjak Anthony Brade B.C. John Cho Andrew Hope Alexander Sun Meredith Giuliani 《Clinical lung cancer》2018,19(2):e219-e226
Introduction
The purpose of this study was to determine the impact of interstitial lung disease (ILD) on radiation pneumonitis (RP) and overall survival (OS) in lung stereotactic body radiation therapy (SBRT).Methods
Patients treated with lung SBRT from 2004 to 2015 were included. Pretreatment computed tomography scans were reviewed and classified for interstitial changes by thoracic radiologists using American Thoracic Society guidelines and Washko and Kazerooni scores. RP was scored prospectively using Common Terminology Criteria for Adverse Events, version 3.0. Pretreatment imaging characteristics, clinical variables, and dosimetry were assessed by univariate (UVA) and multivariate analysis (MVA). OS was assessed by the log-rank test, and the impact of ILD on OS was assessed by Cox regression.Results
Of the 537 patients assessed, 39 had interstitial changes (13 usual interstitial pneumonia [UIP], 24 possible UIP, and 2 inconsistent with UIP). RP was significantly higher in patients with ILD than in patients without ILD (grade ≥ 2, 20.5% vs. 5.8%; P < .01; grade ≥ 3, 10.3% vs. 1.0%; P < .01). Two of 3 grade 5 RP had imaging features of ILD. On UVA, ILD, Washko score, lung parameters performance status, and dose were significant predictors of grade ≥ 2 RP. On MVA, ILD (odds ratio, 5.81; 95% confidence interval, 2.28-14.83; P < .01) and mean lung dose (odds ratio, 1.40; 95% confidence interval, 1.14-1.71; P < .01) were predictors of RP. ILD did not significantly affect OS on UVA or MVA. Median survival was 27.4 months in the ILD cohort and 34.8 in the ILD-negative cohort (P = .17).Discussion
ILD is a significant risk factor for RP in patients treated with lung SBRT. Computed tomography scans should be reviewed for evidence of ILD prior to SBRT. 相似文献7.
Mihai Dorin Vartolomei Matteo Ferro Francesco Cantiello Giuseppe Lucarelli Savino Di Stasi Rodolfo Hurle Giorgio Guazzoni Gian Maria Busetto Ettore De Berardinis Rocco Damiano Sisto Perdona Paolo Verze Roberto La Rocca Marco Borghesi Riccardo Schiavina Eugenio Brunocilla Gilberto L. Almeida Pierluigi Bove Shahrokh F. Shariat 《Clinical genitourinary cancer》2018,16(6):445-452
Introduction
The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non–muscle-invasive bladder cancer (NMIBC).Patients and Methods
The study period was from January 2002 through December 2012. A total of 1046 patients with primary T1 HG/G3 who had NMIBC on re-transurethral bladder resection (TURB) who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance from 13 academic institutions were included. Endpoints were time to disease, and recurrence-free (RFS), progression-free (PFS), overall (OS), and cancer-specific survival (CSS).Results
A total of 512 (48.9%) of patients had NLR ≥ 3 prior to TURB. High pretreatment NLR was associated with female gender and residual T1HG/G3 on re-TURB. The 5-year RFS estimates were 9.4% (95% confidence interval [CI], 6.8%-12.4%) in patients with NLR ≥ 3 compared with 58.8% (95% CI, 54%-63.2%) in patients with NLR < 3; the 5-year PFS estimates were 57.1% (95% CI, 51.5%-62.2%) versus 79.2% (95% CI, 74.7%-83%; P < .0001); the 10-year OS estimates were 63.6% (95% CI, 55%-71%) versus 66.5% (95% CI, 56.8%-74.5%; P = .03); the 10-year CSS estimates were 77.4% (95% CI, 68.4%-84.2%) versus 84.3% (95% CI, 76.6%-89.7%; P = .004). NLR was independently associated with disease recurrence (hazard ratio [HR], 3.34; 95% CI, 2.82-3.95; P < .001), progression (HR, 2.18; 95% CI, 1.71-2.78; P < .001) and CSS (HR, 1.65; 95% CI, 1.02-2.66; P = .03). The addition of NLR to a multivariable model that included established features increased its discrimination for predicting of RFS (+6.9%), PFS (+1.8%), and CSS (+1.7%).Conclusions
Pretreatment NLR ≥ 3 was a strong predictor for RFS, PFS, and CSS in patients with primary T1 HG/G3 NMIBC. It could help in the decision-making regarding intensity of therapy and follow-up. 相似文献8.
Nobuyoshi Takeuchi Shinichi Sakamoto Akira Nishiyama Takuro Horikoshi Yasutaka Yamada Junpei Iizuka Maihulan Maimaiti Yusuke Imamura Koji Kawamura Takashi Imamoto Akira Komiya Yuzuru Ikehara Koichiro Akakura Tomohiko Ichikawa 《Clinical genitourinary cancer》2018,16(4):e817-e829
Background
We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy.Materials and Methods
The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as ≥ 4 and ≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method.Results
The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS ≥ 4 (P = .0031) and ISUP ≥ 3 (P = .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P = .014), and a positive ISUP score was related to prostate-specific antigen level (P = .043), extraprostatic extension (P = .029), and Gleason upgrading (P < .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P < .0001), with a median survival difference of 21 months.Conclusion
Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer. 相似文献9.
Jonathan M. Loree Sean K. Tan Laurence M. Lafond Caroline H. Speers Hagen F. Kennecke Winson Y. Cheung 《Clinical colorectal cancer》2018,17(1):65-72
Background
With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear.Patients and Methods
Using a population-based cohort of mCRC patients who received combination chemotherapy, we aimed to describe the use of IC/MC and their effect on overall survival (OS).Results
Among 617 patients, 120 (19%) had periods of IC, 67 (11%) had periods of MC, and 53 (9%) had periods of both. Most (85.5%) modifications occurred in the first-line setting. The receipt of IC (median OS [mOS], 37 vs. 21 months; P < .0001) or MC (mOS, 36 vs. 24 months; P = .0015) was associated with improved mOS compared with continuous combination therapy. In multivariate analysis adjusting for age, sex, and regimen used at the time of treatment modification, IC (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.42-0.65; P < .0001), MC (HR, 0.71; 95% CI, 0.58-0.88; P = .002), and the combination (HR, 0.45; 95% CI, 0.33-0.63; P < .0001) were all associated with improved mOS. Among patients receiving MC, individuals with (HR, 0.69; 95% CI, 0.53-0.90; P = .005) and without (HR, 0.74; 95% CI, 0.55-1.00; P = .048) re-escalation to their original cytotoxic regimen had improved mOS compared with continuous therapy. The use of IC was associated with an improved OS compared with MC (HR, 0.65; 95% CI, 0.47-0.90; P = .009).Conclusion
In patients with mCRC, IC and MC are reasonable options to maintain quality of life and do not appear to negatively affect OS in carefully selected patients. 相似文献10.
Peter Gibbs Volker Heinemann Navesh K. Sharma Julien Taieb Jens Ricke Marc Peeters Michael Findlay Bridget Robinson Christopher Jackson Andrew Strickland Val Gebski Mark Van Buskirk Huaqing Zhao Guy van Hazel 《Clinical colorectal cancer》2018,17(4):e617-e629
Background
The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone.Patients and Methods
Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side.Results
In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002).Conclusion
The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain. 相似文献11.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献12.
Suresh S. Ramalingam Maurice Pérol Martin Reck Ruben Dario Kowalyszyn Oliver Gautschi Martin Kimmich Eun Kyung Cho Grzegorz Czyzewicz Alexandru Grigorescu Nina Karaseva Shaker Dakhil Pablo Lee Annamaria Zimmerman Andreas Sashegyi Ekaterine Alexandris Gebra Cuyun Carter Katherine B. Winfree Edward B. Garon 《Clinical lung cancer》2018,19(3):270-279.e3
Introduction
Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non–small-cell lung cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff.Patients and Methods
Patients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs).Results
Patients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95% CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab were not as evident; after model adjustment for prognostic factors, OS and PFS HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03), respectively. Age analysis according to quintiles showed HRs favoring ramucirumab for all age groupings. LCSS scores and AEs did not considerably differ between age groups.Conclusion
In this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age. 相似文献13.
Won Kyung Cho Doo Ho Choi Won Park Hyejung Cha Seok Jin Nam Seok Won Kim Jeong Eon Lee Jonghan Yu Young-Hyuck Im Jin Seok Ahn Yeon Hee Park Ji-Yeon Kim Soohyun Ahn 《Clinical breast cancer》2018,18(5):e1141-e1147
Purpose
To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment.Patients and Methods
We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease-free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and < 25 kg/m2 in all patients and in specific subgroups, including tumor subtype, metabolic syndrome, and systemic treatment.Results
In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2? subgroup, DFS and OS were longer in patients with BMI < 25 kg/m2 than ≥ 25 kg/m2 (P = .012 and .005, respectively). In patients with more than one metabolic syndrome, BMI was an unfavorable factor for OS (hazard ratio, 2.669; P < .001)Conclusion
BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2? breast cancer. 相似文献14.
Gerald B. Schulz Tobias Grimm Alexander Buchner Friedrich Jokisch Alexander Kretschmer Jozefina Casuscelli Brigitte Ziegelmüller Christian G. Stief Alexander Karl 《Clinical genitourinary cancer》2018,16(6):e1141-e1149
Background
The purpose of this study was to investigate major complications and risk factors for adverse clinical outcome in surgical high-risk (American Society of Anesthesiologists [ASA] 3-4) patients undergoing radical cystectomy (RC) in a high-volume setting.Patients and Methods
A total of 1206 patients underwent RC between 2004 and 2017 in our institution and were included. We assessed complications graded by the Clavien-Dindo-Classification system (CDC) in addition to the 90-day mortality rate and stratified results by the ASA classification. In a multivariate analysis, risk factors for high-grade complications (CDC ≥ 3) were tested. Additionally, outcome parameters were compared between 2004 to 2010 and 2010 to 2017.Results
Patients with ASA ≥ 3 presented with more locally advanced tumors pT ≥ 3 (52.1% vs. 42.4%; P = .002) and positive lymphatic spread N1 (27.2% vs. 23.5%; P = .001) compared with patients with ASA ≤ 2. High-grade complications were significantly (P < .001) more prevalent in patients with ASA ≥ 3 compared with patients with ASA ≤ 2: CDC3 (14.6% vs. 9.4%), CDC4 (10.2% vs. 5.4%), and CDC5 (2.5% vs. 1.0%). The 90-day mortality rate (7.6% vs. 3.2%; P = .002) and perioperative reinterventions (23.5% vs. 13.1%; P < .001) were elevated in patients with ASA ≥ 3. ASA (odds ratio [OR], 2.701, 95% confidence interval [CI], 1.089-6.703; P = .032), previous abdominal operations (OR, 1.683; 95% CI, 1.188-2.384; P = .003), and body mass index ≥ 30 (OR, 1.533; 95% CI, 1.021-2.304; P = .039) proved to function as independent predictors for major complications. CDC ≥ 3 complications (31.7% vs. 24.3%; P = .029) and 90-day mortality (10.4% vs. 5.6%; P = .018) were significantly lower in the second half of the study period.Conclusions
Mortality and morbidity in surgical high-risk patients with ASA 3 to 4 undergoing RC is about twice as high compared with patients with ASA 1 to 2. ASA, previous abdominal operations, and elevated body mass index independently predict adverse clinical outcome in patients with ASA 3 to 4. Our results may help to weigh the surgical risk of RC in multimorbid patients. 相似文献15.
Annelies Verbiest Diether Lambrechts Thomas Van Brussel Gabrielle Couchy Agnieszka Wozniak Arnaud Méjean Evelyne Lerut Stéphane Oudard Virginie Verkarre Sylvie Job Aurélien de Reynies Jean-Pascal Machiels Jean-Jacques Patard Jessica Zucman-Rossi Benoit Beuselinck 《Clinical genitourinary cancer》2018,16(4):266-273
Background
Clear-cell renal-cell carcinoma (ccRCC) is characterized by loss of a functional Von Hippel–Lindau (VHL) protein. We investigated the potential of 3 single nucleotide polymorphisms (SNPs) in VHL as biomarkers in metastatic ccRCC (m-ccRCC) patients treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).Patients and Methods
We genotyped 3 VHL SNPs in 199 m-ccRCC patients: rs1642742 T > C, rs1642743 A > G, and rs1678607 C > A. Primary end points were response rate (RR), progression-free survival (PFS), and overall survival (OS) after start of first-line TKI. RR was compared with Fisher’s exact test, and PFS and OS with Kaplan-Meier analysis and multivariable Cox regression. Secondary end points were association with VHL promotor hypermethylation, VHL mutation status, VHL loss of heterozygosity, ≥ 25% sarcomatoid dedifferentiation, and expression of genes implicated in angiogenesis and immunoresponse (Fisher’s exact test and unpaired t tests).Results
The minor alleles of rs1642742 and rs1642743, known to be in close linkage disequilibrium, were associated with poor outcome, following a recessive pattern. For the rs1642742 CC versus TT/TC genotype, OS was 11 versus 26 months (hazard ratio = 2.3; 95% confidence interval, 1.2-6.6; P = .015). For the rs1642743 GG versus AA/AG genotype, OS was 15 versus 28 months (hazard ratio = 2.6; 95% confidence interval, 1.4-5.0; P = .004). After multivariable analysis, both remained linked with poor OS (P = .018 and P = .009, respectively). There was a trend toward shorter PFS and poorer RR. Both SNPs were associated with ≥ 25% sarcomatoid dedifferentiation (P = .037 and .006, respectively). No significant results were found for rs1678607.Conclusion
rs1642742 and rs1642743 are candidate biomarkers for poor OS in m-ccRCC patients receiving first-line VEGFR-TKI. They are associated with higher levels of sarcomatoid dedifferentiation. 相似文献16.
Y.-K. Chao W.-Y. Chuang H.-K. Chang C.-K. Tseng C.-J. Yeh Y.-H. Liu 《European journal of surgical oncology》2017,43(1):234-239
Background
The purpose of this study was to investigate the prognosis and its predictors in patients with esophageal squamous cell carcinoma (ESCC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT).Methods
We examined a total of 187 ESCC patients who achieved MaHR following nCRT and survived the perioperative period. MaHR was defined as either absence or <10% vital residual tumor cells (VRTC) in the resected esophagus without nodal involvement. Univariate and multivariate analyses were used to identify factors significantly associated with overall survival (OS).Results
At the time of analysis, 113 patients (60.4%) were dead (5-year OS = 48%; median survival time = 54.8 months). The amount of VRTC (1–10% versus 0% VRTC; hazard ratio [HR] = 1.9, P < 0.001) and the thoroughness of histopathological examination (standard [≤ 4 tumor blocks] versus thorough [> 4 tumor blocks], HR = 1.57; P = 0.013) were independent predictors of OS in multivariate analysis. A stepwise increase in OS was observed in the following groups: patients with 1–10% VRTC identified by the standard protocol, patients with 1–10% VRTC identified by the thorough protocol, patients with 0% VRTC identified by the standard protocol, and patients with 0% VRTC identified by the thorough protocol (5-year OS rates = 20%, 40%, 50%, and 62%, respectively, P < 0.001).Conclusions
In ESCC patients who achieve MaHR after nCRT, the presence of microscopical residual disease and the thoroughness of histopathological examination are associated with survival. 相似文献17.
Chung Ryul Oh Jeong Eun Kim Jihoon Kang Sun Young Kim Kyu-pyo Kim Yong Sang Hong Seok-Byung Lim Chang Sik Yu Jin Cheon Kim Jihun Kim Se Jin Jang Tae Won Kim 《Clinical colorectal cancer》2018,17(4):e679-e685
Background
We investigated whether the microsatellite instability (MSI) status affects the survival outcomes in patients with stage II/III rectal cancer who have undergone an upfront curative resection.Patients and Methods
A total of 1103 patients with curatively resected stage II/III rectal cancer who had available polymerase chain reaction-based MSI results were included in the final analysis.Results
Twenty-four (2.2%) patients in the total cohort were found to be MSI-high (MSI-H). In univariate analysis, neither disease-free survival (DFS) nor overall survival (OS) demonstrated significant differences between patients with MSI-H tumors and those with MSI-low (MSI-L) or microsatellite stable (MSS) tumors. The 5-year DFS rate was 78.0% in MSI-H patients and 69.9% in MSI-L/MSS patients (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.35-2.02; P = .689). The 5-year OS rates for MSI-H and MSI-L/MSS patients were 84.0% and 83.1%, respectively (HR, 0.86; 95% CI, 0.27-2.69; P = .790). By multivariate analysis, the MSI status did not affect either the DFS (HR, 1.00; 95% CI, 0.40-2.47; P = .994) or OS (HR, 0.85; 95% CI, 0.26-2.73; P = .778).Conclusions
MSI-H tumors are rarely observed in rectal adenocarcinoma, and the MSI status may not affect the survival outcome in patients with a resected rectal cancer. 相似文献18.
Shaan Dudani Xiaofu Zhu Daniel W. Yokom Andrew Yamada Cheryl Ho Jason R. Pantarotto Natasha B. Leighl Tinghua Zhang Paul Wheatley-Price 《Clinical lung cancer》2018,19(1):e11-e18
Introduction
Standard management of stage II non–small-cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. We examined outcomes in this defined patient group.Methods
We reviewed the records of patients with stage II NSCLC treated nonsurgically with curative intent from 2002 to 2012 across 3 academic cancer centers. Data collected included demographics, comorbidities, staging, treatments, and survival. The primary endpoint was overall survival (OS). We assessed factors associated with treatment choice and OS.Results
A total of 158 patients were included: the median age was 74 years (range, 50-91 years), 44% were female, and 68% had a performance status of 0 to 1. The stage II groupings of the patients were T2b-T3 N0 in 55% and N1 in 45%. The most common reasons for inoperability were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median, 60 Gy [range, 48-75 Gy]). Seventy-three percent received RT alone; 24% received concurrent and 3% sequential chemoradiotherapy (CRT). In multivariate analyses, CRT was less likely in older patients (≥ 70 years) (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.70; P = .006) and in patients with higher (> 5) Charlson comorbidity scores (OR, 0.34; 95% CI, 0.13-0.90; P = .03) or normal (< 10 × 109/L) white blood cell counts (OR, 0.26; 95% CI, 0.09-0.73; P = .01). At the time of our analysis, 74% have died. The median OS was 22.9 months (range, 17.1-26.6 months). Patients who had undergone CRT had a significantly longer median OS than those receiving RT alone (39.1 vs. 20.5 months; P = .0019), confirmed in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; P = .001).Conclusion
Nonsurgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared with RT alone. A randomized trial may be warranted. 相似文献19.
D.R. Henderson J.R. Murray S.L. Gulliford A.C. Tree K.J. Harrington N.J. Van As 《Clinical oncology (Royal College of Radiologists (Great Britain))》2018,30(9):539-547
Aims
There are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose–volume histograms (DVHs) and dose–surface maps (DSMs).Materials and methods
Urinary bladder trigone and rectum DSMs were produced for a single-institution service evaluation cohort of 50 patients receiving SBRT for localised prostate cancer, together with conventional DVHs for bladder and rectum. Patients had been prospectively recruited to this cohort and treated according to a pre-defined protocol to a dose of 36.25 Gy in five fractions. Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) toxicity data were recorded prospectively. Logistic regression was used to identify dosimetric predictors of acute IPSS+10 (rise of 10 points or more above baseline) and grade 2+ RTOG toxicity.Results
On univariate analysis, trigone area receiving 40 Gy and trigone Dmax were associated with IPSS+10 (odds ratio 1.06 [1.02–1.11], P = 0.007 and odds ratio 1.54 [1.06–2.25], P = 0.024, respectively). These two variables were highly correlated. In a multivariate model, including all baseline variables, trigone Dmax remained associated with IPSS+10 (odds ratio 1.91 [1.13–3.22], P = 0.016). These findings were not significant with Holm–Bonferroni correction for multiple testing (corrected P value threshold 0.006). No associations were seen between rectal toxicity and DVH or DSM parameters.Conclusions
Our study suggests a potential relationship between high doses to the urinary bladder trigone and patient-reported urinary toxicity in prostate SBRT, and is consistent with previous studies in conventionally fractionated radiotherapy, justifying further evaluation in larger cohorts. 相似文献20.
Neelima Denduluri Gary H. Lyman Yunfei Wang Phuong Khanh Morrow Richard Barron Debra Patt Debajyoti Bhowmik Xiaoyan Li Menaka Bhor Patricia Fox Rahul Dhanda Shanmugapriya Saravanan Xiaolong Jiao Jacob Garcia Jeffrey Crawford 《Clinical breast cancer》2018,18(5):380-386