Abstract Background Recent evidence indicates that tumor progression involves factors of systemic inflammation, such as platelets and lymphocytes. In this study, we investigated the prognostic ...relevance of the preoperative platelet to lymphocyte (P/L) ratio on time to recurrence (TTR) and overall survival (OS) in patients with stage II and III colon cancer (CC) who underwent curative resection. Methods In this retrospective study, 372 CC patients were included. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS. Results In univariate analysis, the elevated P/L ratio was significantly associated with decreased TTR (HR = 1.60, 95% CI = 1.02 to 2.51, P = .040) and remained significant in multivariate analysis (HR = 1.65, 95% CI = 1.05 to 2.58, P = .030), where HR and CI represent Hazard ratio and confidence interval, respectively. Patients with elevated P/L ratio showed a median TTR of 116 months. In contrast, patients with low P/L ratio had a median TTR of 132 months. In OS analysis, the elevated P/L ratio showed a trend toward decreased OS in univariate analysis (HR = 1.54, 95% CI = .95 to 2.48, P = .079). Conclusion In this study, we identified the preoperative P/L ratio as a prognostic marker for TTR in stage II and III CC patients.
Abstract Background Inflammation plays an important role in tumor proliferation and survival in cancer patients. The aim of this study was to investigate the prognostic impact of the ...pre-operative–derived neutrophil/lymphocyte ratio (dNLR) in a large cohort of soft tissue sarcoma (STS) patients after curative surgical resection. Methods The impact of preoperative dNLR on disease-free survival (DFS) and overall survival (OS) in retrospectively evaluated 340 STS patients was assessed using Kaplan–Meier curves and Cox proportional models. Results Applying receiver operating curve analysis, we determined a cut-off value of 2.39 for the dNLR to be optimal for discrimination of patients' survival in the whole cohort. Kaplan–Meier curves revealed a dNLR greater than or equal to 2.39 as a marker for decreased DFS ( P = .031) and OS ( P = .007, log-rank test) in STS patients. In multivariate analysis, increased dNLR was significantly associated with poor OS (hazard ratio 1.60, 95% confidence interval 1.07 to 2.40, P = .022). Conclusions This study demonstrates that preoperative dNLR might represent a well-correlated surrogate marker for the widely validated NLR. The dNLR is easily obtainable and can provide important information for individual risk assessment in clinical trials.
Aromatase inhibitors are effective as endocrine treatment for patients with hormone receptor-positive breast cancer. According to the hypothesis that overweight patients have higher levels of ...aromatase enzyme availability, we investigated the influence of body mass index (BMI) on the efficacy of adjuvant endocrine therapy in premenopausal patients in a retrospective analysis of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 trial.
ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg subcutaneously every 28 days) in combination with anastrozole or tamoxifen with or without zoledronic acid (4 mg intravenously every 6 months) in premenopausal women with endocrine-responsive breast cancer. BMI was calculated using the prospectively collected data on patients' height and weight at study entry. BMI categories have been differentiated according to the WHO definition.
Overweight patients treated with anastrozole had a 60% increase in the risk of disease recurrence (hazard ratio HR, 1.60; 95% CI, 1.06 to 2.41; P = .02) and more than a doubling in the risk of death (HR, 2.14; 95% CI, 1.17 to 3.92; P = .01) compared with normal weight patients treated with anastrozole. In the overweight group, patients treated with anastrozole had a nearly 50% increase in the risk of disease recurrence (HR, 1.49; 95% CI, 0.93 to 2.38; P = .08) and a three-fold increase in the risk of death (HR, 3.03; 95% CI, 1.35 to 6.82; P = .004) compared with patients treated with tamoxifen.
BMI significantly impacts on the efficacy of anastrozole plus goserelin in premenopausal patients with breast cancer, probably through influencing aromatase availability and/or ovarian suppression by goserelin.
With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer ...types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.
Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.
We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients' survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01-1.51, p = 0.041) was identified.
In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk ...model.
In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich.
Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p<0.0001). As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence): cS IA-B 8/463 patients (1.7%), cS IS-IIB 5/86 patients (5.9%), cS IIC 3/21 patients (14.3%) and cS IIIA-C 15/70 patients (21.4%). This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence): cS IA-B (0.5%), cS IS-IIB (6.0%), cS IIC (11.1%) and cS IIIA-C (19.1%). Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier) which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007).
According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy ...and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting. Methods ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3·6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3·6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646. Findings 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (−11·3%, mean difference −0·119 g/cm2 95% CI −0·146 to −0·091, p<0·0001) and trochanter (−7·3%, mean difference −0·053 g/cm2 −0·076 to −0·030, p<0·0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (−13·6%, mean difference −0·141 g/cm2 −0·179 to −0·102 vs −9·0%, mean difference −0·095 g/cm2 −0·134 to −0·057, p<0·0001 for both). 2 years after the completion of treatment (median follow-up 60 months range 15·5–96·6), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine −6·3%, mean difference −0·067 g/cm2 −0·106 to −0·027, p=0·001; trochanter −4·1%, mean difference −0·03 g/cm2 −0·062 to 0·001, p=0·058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0·4%, mean difference 0·004 g/cm2 −0·024 to 0·032; trochanter +0·8%, mean difference 0·006 g/cm2 −0·018 to 0·028) and increased BMD at 60 months at both sites (lumbar spine +4·0%, mean difference 0·039 g/cm2 0·005–0·075, p=0·02; trochanter +3·9%, mean difference 0·028 g/cm2 0·003–0·058, p=0·07) compared with baseline. Interpretation Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years. Funding AstraZeneca (London, UK) and Novartis (Basel, Switzerland).
Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. ...In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.
Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models.
Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25-0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23-0.51, p<0.001).
The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid ...(UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC.
Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated.
None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077-1.751; p = 0.011).
In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer. The ABCSG-8 ...(Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients.
Endocrine receptor-positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated.
Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio HR, 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment.
Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.
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