Predictor Of Better Survival Research Articles

CUP Syndrome in Neuroendocrine Neoplasia: Analysis of Risk Factors and Impact of Surgical Intervention.

Neuroendocrine neoplasia (NEN) with unknown primary site (NEN-CUP tumors) may have a poor prognosis. We evaluated the clinical presentation, therapy, outcome, and risk factors for adverse outcomes in patients who had these tumors. In 243 patients who had NEN, a retrospective review was performed in 38 patients who had NEN-CUP tumors. The 38 patients who had NEN-CUP tumors were evaluated in three groups: group 1 (surgery; primary tumor detected; ten patients); group 2 (surgery; no primary tumor detected; ten patients); and group 3 (no surgery; 18 patients). Risk factors were evaluated with univariate and multivariate analyses. Most patients who had NEN-CUP tumors [32 patients (84%)] had World Health Organization (WHO) performance score of 0 or 1, and most tumors [24 patients (63%)] were well differentiated (WHO grade, G1 or G2; Ki-67 index, ≤20%). Univariate analysis showed that greater survival was significantly associated with lower patient age, lower WHO performance score, lower WHO grade, lower number of metastatic sites, treatment with surgery, and no treatment with chemotherapy. Multivariate analysis showed that low WHO performance score (hazard ratio 7.63, 95% confidence interval (CI) 2.63-22.19) and treatment with surgery (hazard ratio 0.10, CI 0.028-0.381) were significant independent predictors of improved survival. In patients with NEN-CUP tumors, surgical treatment is an independent predictor of better survival. Therefore, surgical treatment may be indicated in patients with good general health status and well-differentiated NEN-CUP tumors.

Palliative therapy for esophageal cancer: laser therapy alone is associated with a better functional outcome.

The aim of our study was to compare functional outcome and survival in patients who underwent laser therapy (LT) or laser therapy and esophageal stenting (LTES) to palliate inoperable esophageal cancer. Two hundred and twenty-seven consecutive patients who had endoscopic palliation for esophageal cancer were enrolled in this retrospective study. One hundred and sixty-four underwent LT alone and 63 had LTES. A dysphagia score was adopted (0: absolute dysphagia; 1: liquid diet; 2: semisolid diet; 3: free diet). Survival analysis and non parametric statistics were performed. Patients in the LTES group reported a significantly worse dysphagia score than LT patients (p<0.01). LTES patients more frequently reported difficulty swallowing than LT patients (p<0.01). No difference between LTES and LT groups was observed in terms of overall survival. Only radiotherapy resulted in a significant predictor of better survival (p=0.007). Despite a similar survival, LTES is a predictor of a worse functional palliation than LT alone. Radiotherapy was associated with better survival in patients treated with LT. Therefore, these data seem to suggest that a combination of endoscopic LT and external radiotherapy may yield the best results in palliative care of advanced esophageal cancer.

0210: Long term follow up of cardiomyopathy in Friedreich Ataxia

Friedreich Ataxia (FRDA) is an autosomal recessive cerebellar ataxia, caused by GAA expansion in frataxin gene. Hypertrophic cardiomyopathy is usual in FRDA and cardiac complications are the first cause of death. From 1990 to 2012, we studied 141 patients with genetically confirmed FRDA. Mean age was 30±10y (mean±sd), 54% were female, age at onset 16±8y, disease duration 15±8y and 74% were wheelchair users.Mean length of short GAA expansion was 1,85±0,7Kb and of longer allele 2.6±0.7Kb.Each patient underwent clinical examination, electrocardiogram and echocardiography. 9% had chest pain, 2,8% dyspnea and 9% palpitations. ECG presented T wave abnormalities (88%). 3 patients had atrial fibrillation (AF).LV interventricular septal wall thickness (IVS) was 12±3mm, LV posterior wall thickness (PW) =11±2mm, LV diastolic diameter (EDD) = 43±5mm, LV systolic diameter (ESD) =25±5mm and indexed LV mass (LVMi) =103±31g/m², LV ejection fraction (EF) = 67±7%. News were obtained in 2013, no patient was lost of follow-up. After a median follow up of 12±5y, 16 deaths occurred and 1 patient was transplanted (38±10y). 26 patients (18%) experienced AF (34±10y), 14 (10%) heart failure (36±12y) and 15 (11%) had EF<50% (33±11y). In univariate analysis, the predictors of survival were: short GAA (p<0.0001), age of onset (p=0.0002), ESD (p=0.002), IVS (p=0.0087), EF (p=0.0001) and LVMi (p=0.01). In multivariate analysis, only short GAA (p=0.001), EF (p=0.01) and LVMi (p=0.008) were independent predictors of survival. Short GAA and LVMi remained independent predictors of the first cardiac events in multivariate analysis (p=0.0002, and p=0.0003 respectively). GAA repeats are the best predictors of survival and cardiac events in FRDA patients, but EF and LV mass are also predictors of long term evolution suggesting the importance of cardiac management in Friedreich ataxia.

Physiological predictors of long-term survival in juvenile Steller sea lions (Eumetopias jubatus).

This study builds on a continued effort to document potential long-term research impacts on the individual, as well as to identify potential markers of survival for use in a field framework. The Transient Juvenile Steller sea lion (TJ) project was developed as a novel framework to gain access to wild individuals. We used three analyses to evaluate and predict long-term survival in temporarily captive sea lions (n = 45) through Cormack-Jolly-Seber open population modelling techniques. The first analysis investigated survival in relation to the observed responses to handling stress through changes in six principal blood parameters over the duration of captivity. The second analysis evaluated survival compared with body condition and mass at entry and exit from captivity. Finally, the third analysis sought to evaluate the efficacy of single-point sampling to project similar survival trends for use in field sampling operations. Results from a priori models ranked through Akaike information criterion model selection methods indicated that mass gains (4.2 ± 12%) over captivity and increases in leucocytes (WBC, 1.01 ± 3.54 × 10(3)/mm(3)) resulted in a higher average survival rate (>3 years). Minor support was identified for the single-point measures of exit mass and entry WBC. A higher exit mass predicted a higher survival rate, whereas a higher WBC predicted a lower survival rate. While changes in mass and WBC appear to be the best predictors of survival when measured as a change over time, single-point sampling may still be an effective way to improve estimates of population health.

The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis.

PurposeThe value of insulin-like growth factor 1 receptor (IGF-1R) for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R.MethodsStudies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs) for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs) were estimated using fixed- or random-effects models according to between-study heterogeneity.ResultsTen studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS), three studies the impact on breast cancer-specific survival (BCSS), and seven studies the impact on disease-free survival (DFS). The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42–0.95, P=0.03), indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35–0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35–0.85, P=0.008, respectively). The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was correlated with favorable DFS (combined HR: 0.61, 95% CI: 0.41–0.92, P=0.02) and OS/BCSS (combined HR: 0.73, 95% CI: 0.57–0.93, P=0.01). Membranous IGF-1R positivity in triple-negative breast cancer predicted worse DFS (combined HR: 1.86, 95% CI: 1.03–3.34, P=0.04). Membranous IGF-1R positivity in Her-2-positive or ER (estrogen receptor)-negative breast cancer was not found to be a significant prognostic indicator.ConclusionThe results of this meta-analysis suggest that IGF-1R expression has different prognostic values for patients with breast cancers of different molecular subtypes. It was a favorable prognostic indicator in unselected breast cancers and hormone-receptor-positive cancers, but indicated poor survival in triple-negative breast cancers.

Flow-Cytometry MRD Evaluation in Children with ALL; Can MRD Level on Day 33 Serve As a Surrogate Marker for Relapse?

Treatment-response assessment via quantification of MRD has become a corner-stone for risk stratification in childhood ALL. Although MRD has been shown to retain independent prognostic significance, the relationship with other prognostic variables has been incompletely explored. Moreover, determination of the most reliable treatment time-point for FCM-MRD evaluation that would serve as the best surrogate marker in predicting relapse, is still an issue of debate. To determine the utility of sequential measurements of FCM-MRD, with specific emphasis on day 33 and its correlation with known prognostic factors and outcome, we retrospectively analyzed the results of FCM-MRD study/data of 825 bone marrow samples of 133 children with ALL, at different treatment time-points, during induction and early consolidation (days 15, 33, 78, week 22-24, at start and at the end of maintenance therapy). All patients were homogeneously treated on BFM-based protocols and prognostic groups were defined by sex, WBC, prednisone response, risk-group allocation, immunophenotype and ETV6/RUNX1-presence. We investigated: a) the relationship between relapse probability and known prognostic factors like age, sex, WBC, immunophenotype, prednisone-response, ETV6/RUNX1 translocation, CDKN2A/2B deletion, hyperdiploidy, protocol risk-group, MRD(constant variable) and MRD positivity(≥0.1% vs <0.1%)(Kaplan-Meier and lïgrank test), b) the correlation between MRD(+) and outcome (OS and EFS, Kaplan-Meier). Additionally, multivariable Cox-models were used to determine the impact of MRD and WBC, sex, age, prednisone-response, on OS and EFS.Patients with MRD≥0.1% at the end of induction (day 33) were estimated with 5-year RFS rates of only 60.0±12.8%, compared to MRD low(<0.1%)/negative patients that enjoyed superior 5-year RFS rates of 91.3±3.0%. Both days 15 and 33 of FCM-MRD positivity maintained a significant prognostic impact on the incidence of relapse within all subgroups. MRD(+)d15 and MRD(+)d33 detection combined, appeared to have a statistically significant impact on survival probability (RFS 65.9%±10.6, p<0.001). Additionally, FCM-MRD on day 33 was notably more strongly associated with used prognostic factors, while we were able to demonstrate that FCM-MRD log-reduction rates between days 15 and 33 can also be added as an important relapse prediction marker, apart from absolute MRD quantifications.In our study, MRD(+)d15 and MRD(+)d33 in combination, strongly and statistically significant correlated with survival probability. Additionally, we propose the FCM-MRD log-reduction rate between days 15 and 33 and end-induction evaluation(day 33) as better predictors of survival and relapse probability, than only day 15 FCM-MRD estimations. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hepatology Highlights

Hepatology Highlights

Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes.

The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication.

Molecular monitoring and mutations in chronic myeloid leukemia: how to get the most out of your tyrosine kinase inhibitor.

The course of chronic myeloid leukemia (CML) and the response to treatment with tyrosine kinase inhibitors (TKIs) are best monitored and assessed using two molecular tests: the first is real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR), which measures the size of residual disease that is expressed as BCR-ABL1% (the ratio between BCR-ABL1 and a control gene) and the other is mutational analysis by Sanger sequencing, which checks for the presence of BCR-ABL1 kinase domain point mutations. Both tests are technically demanding and require a high level of specialization and standardization. RQ-PCR, when performed on a regular basis, allows for the defining of molecular response (MR) levels as log reduction from a standardized baseline: major molecular response (MMR or MR(3)) that is the best predictor of survival; and the deeper molecular response (MR(4), MR(4.5), and MR(5)) that is necessary to enroll a patient in a trial aiming at treatment-free remission (TFR). Mutational analysis, to be performed in case of failure or warning by Sanger sequencing, allows for screening of the BCR-ABL1 kinase domain for mutations conferring resistance to TKIs. Since different mutations have different degrees of sensitivity to each of the currently available TKI, the knowledge of BCR-ABL1 kinase domain-mutation status is necessary for subsequent treatment choice. Optimal patient management requires that MR and mutational information be rationally interpreted at both the technical and at the biologic level, and put into context-therapeutic decisions also take into account other factors, such as age, comorbidities, side effects, compliance, and treatment-related complications.

The End of the Beginning: Circulating Tumor Cells As a Biomarker in Castration-Resistant Prostate Cancer

Although circulating tumor cells (CTCs) were first observed from patients with metastatic malignancies more than 100 years ago, only recently has the clinical and research potential of CTCs become widely recognized. Because CTCs are thought to represent cells that are shed by primary or metastatic tumors, significant interest has focused on examining CTCs as prognostic or predictive biomarkers in several malignancies, including breast and prostate cancer. One could hypothesize that the number of CTCs could be prognostically important by potentially estimating the total-body burden of disease and/or a tumor’s invasiveness. Alternatively, changes in CTC counts might indicate sensitivity or resistance to an anticancer therapy. CTCs could also represent research tools to personalize treatment by serving as a so-called liquid biopsy of an individual’s disease. Quantitation and characterization of CTCs may therefore represent a means to directly inform clinical care but also serve as an investigational platform to elucidate basic mechanisms of tumor biology. The most extensively studied clinical role for CTCs is as a prognostic biomarker; that is, counts at a specific time point are associated with a later discrete clinical end point. In this capacity, CTC counts that are enumerated using the CellSearch platform (Veridex, Raritan, NJ) are the most studied. CellSearch enriches for CTCs with antibodies directed against the epithelial cell adhesion molecule (EpCAM), which is expressed on epithelially derived cells. CTCs are then identified and quantitated on the basis of nuclear staining with 4,6diamidino-2-phenylindole (DAPI), and anticytokeratin and antiCD45 antibodies, which distinguishes CD45 epithelial cells from CD45 leukocytes. In clinical trials, CellSearch CTC counts are prognostic for overall survival (OS) in metastatic breast, colon, and prostate cancers. In prostate cancer, specifically, the Circulating Tumor Cells and the Prediction of Overall Survival in Patients With Androgen Independent Prostate Cancer Entering Onto Chemotherapy (IMMC38) study demonstrated the prognostic value of CellSearch CTCs in 238 men with metastatic castration-resistant disease (mCRPC) starting a new first, second, or third line of chemotherapy. In this study, a pretreatment CTC threshold of 5 CTCs/7.5 mL of blood distinguished patients into favorable and unfavorable groups, the latter having shorter median OS (11.5 v 21.7 months; hazard ratio, 3.3; P .001). In their modeling, the best predictor of survival incorporated baseline high-serum lactate dehydrogenase (LDH) levels with baseline CTC counts; the addition of prostate-specific antigen (PSA) did not improve prediction of survival. In patients with unfavorable baseline counts, conversion to a favorable count after the initiation of treatment was also associated with improved survival. Conversely, conversion to unfavorable counts after treatment initiation was associated with worse survival. Perhaps most importantly, CTC counts outperformed PSA in predicting survival at all time points. More recently, the prognostic value of 5 CTCs/7.5 mL of blood (with the CellSearch assay) was confirmed in a randomized phase III study of abiraterone acetate, a novel hormonal therapy, in men with mCRPC who were previously treated with docetaxel. In this study, CTCs were enumerated at baseline and during the first three cycles. CTC conversion from 5 CTCs to 5 CTCs, along with changes in serum LDH, was strongly predictive of OS. Similar results were recently observed in a phase III study of docetaxel with or without lenalidomide. Building on these findings, in the article that accompanies this editorial, Goldkorn et al present an analysis of the impact of baseline and post-treatment CTC counts on OS and disease response in a subset of men with mCRPC who were treated as part of the Southwest Oncology Group (SWOG) trial 0421, a phase III study comparing the effectiveness of docetaxel plus atrasentan, an endothelin receptor antagonist, versus docetaxel alone. The study itself failed to meet its coprimary end points of improved OS and progression-free survival with the addition of atrasentan and was halted early for futility. Nevertheless, as part of the study, CTCs were enumerated at baseline and 21 days after the first dose of the study treatment. In contrast to the IMMC-38 study, this study had a uniform cohort of men with chemotherapy-naive CRPC and a longer duration of median follow-up (24 v 16 months). In their analysis, the authors showed that baseline CTC counts were correlated with recognized prognostic markers, including PSA, alkaline phosphatase, bone pain, liver disease, and hemoglobin, although relationship with LDH, a widely recognized prognostic marker, was not assessed. Baseline CTC count was associated with subsequent PSA declines and with objective responses. Importantly, median survival for patients with 5 CTCs/7.5 mL of blood at baseline was far better than for those with 5 CTCs (26 v 13 months), and after adjustment for known prognostic factors, the baseline CTC JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 11 APRIL 1

Primary chest wall chondrosarcomas: results of surgical resection and analysis of prognostic factors

Wide surgical excision with tumour-free margins is the mainstay of therapy for primary chest wall chondrosarcoma (PCWC). Few studies on treatment outcome and prognostic factors of PCWC requiring chest wall resection are available. We analysed our experience on surgical treatment of PCWC with emphasis on survival and recurrence prognostic factors. From 1986 to 2012, 89 patients (65.2% males, median age 55 years) with PCWC were operated on. The median tumour maximum diameter was 7 cm (range 2-30 cm). We performed 23 sternectomies and 66 lateral chest wall resections (median ribs resected: 2; range 1-7). Resections were extended to lung (n = 19), diaphragm (n = 13), vertebral body (n = 6) or clavicle (n = 1). Negative margins were obtained in 85.4% of cases. Chest wall reconstruction was obtained mainly by prosthetic non-rigid or rigid materials and muscle flap coverage. In the last years, 3 patients received a sternal replacement with cadaveric allograft, and 2 had a chest wall reconstruction with titanium bars and 17 with a rib-like prosthesis. Perioperative mortality and morbidity rates were 0 and 12.4%, and 5- and 10-year overall and disease-free (on R0 resections) survival rates were 67.1 and 57.8%, and 70 and 52%, respectively. A favourable outcome (univariate analysis) was seen for G1 tumours (P < 0.0001), negative surgical margins (P < 0.0001), age ≤55 years (P = 0.005), no adjuvant treatment (P < 0.001) and diameter ≤6 cm (P = 0.005). Independent predictors of better survival (multivariate analysis) were negative surgical margins (P = 0.0001), G1 tumours (P = 0.02), age ≤55 years (P = 0.006) and diameter ≤6 cm (P = 0.006). A predictive risk factor for recurrence was histological grade. Surgical resection of PCWC leads to good oncological outcome. Wide surgical margins and G1 tumours predicted a better prognosis and a lower recurrence rate. The evolution of surgical technique and the introduction in clinical practice of new prosthetic materials allowed larger resections, and safe and anatomical reconstruction.

Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

BackgroundMetabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated.MethodsClinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed.ResultsMetabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis).ConclusionsMetabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

A fully automatic extraction of magnetic resonance image features in glioblastoma patients

Glioblastoma is the most common malignant brain tumor. It is characterized by low median survival time and high survival variability. Survival prognosis for glioblastoma is very important for optimized treatment planning. Imaging features observed in magnetic resonance (MR) images were shown to be a good predictor of survival. However, manual assessment of MR features is time-consuming and can be associated with a high inter-reader variability as well as inaccuracies in the assessment. In response to this limitation, the authors proposed and evaluated a computer algorithm that extracts important MR image features in a fully automatic manner. The algorithm first automatically segmented the available volumes into a background region and four tumor regions. Then, it extracted ten features from the segmented MR imaging volumes, some of which were previously indicated as predictive of clinical outcomes. To evaluate the algorithm, the authors compared the extracted features for 73 glioblastoma patients to the reference standard established by manual segmentation of the tumors. The experiments showed that their algorithm was able to extract most of the image features with moderate to high accuracy. High correlation coefficients between the automatically extracted value and reference standard were observed for the tumor location, minor and major axis length as well as tumor volume. Moderately high correlation coefficients were also observed for proportion of enhancing tumor, proportion of necrosis, and thickness of enhancing margin. The correlation coefficients for all these features were statistically significant (p < 0.0001). The authors proposed and evaluated an algorithm that, given a set of MR volumes of a glioblastoma patient, is able to extract MR image features that correlate well with their reference standard. Future studies will evaluate how well the computer-extracted features predict survival.

Predictive value of exercise myocardial perfusion imaging in the Medicare population: the impact of the ability to exercise.

Although the prognostic value of quantitative single photon emission computed tomography myocardial perfusion imaging (MPI) with exercise and pharmacologic stress is well established, the prognostic and management value in the Medicare age population is less clear. The prospectively populated Cleveland Clinic nuclear cardiology database was used to identify 5,994 consecutive pateints, age >65 years [1,664 (28%) exercise MPI, mean age 72.4±5.1, 74% male], who underwent MPI between January 2004 and January 2008. Clinical baseline variables, post test 90 days revascularization and MPI variables were analyzed. Overall and stratified nonparametric survival estimates were obtained by Kaplan-Meier method. Median follow-up time was 2.4 years. Parametric hazard modeling with bootstrap bagging methods was used to determine prognostic variables predicting mortality. There was no difference in mortality in patients with an abnormal MPI vs. those with normal MPI. Amongst the patients who underwent exercise MPI, there were 103 (6%) deaths and 121 (8.2%) revascularizations. Only lower exercise capacity (<7 METs) and higher end systolic volume (ESV) predicted mortality. Although a larger amount of ischemia influenced down stream revascularization ischemia, revascularization of patients with an abnormal exercise MPI did not offer a survival benefit (log rank P value=0.01). In the a Medicare age population, exercise MPI perfusion variables influenced rates of revascularization but failed to provide incremental significant risk-stratification beyond exercise capacity. Maximum METs achieved appears to be a better predictor of survival.

TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients

Background:Transforming growth factor β-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC. In order to validate and extend these results, we broaden the analysis and studied TGFBI expression in a large series of samples obtained from stage I–IV NSCLC patients.Methods:TGFBI expression was assessed by immunohistochemistry in 364 completely resected primary NSCLC samples: 242 adenocarcinomas (ADCs) and 122 squamous cell carcinomas (SCCs). Kaplan–Meier curves, log-rank tests and the Cox proportional hazards model were used to analyse the association between TGFBI expression and survival.Results:High TGFBI levels were associated with longer overall survival (OS, P<0.001) and progression-free survival (PFS, P<0.001) in SCC patients who received adjuvant platinium-based chemotherapy. Moreover, multivariate analysis demonstrated that high TGFBI expression is an independent predictor of better survival in patients (OS: P=0.030 and PFS: P=0.026).Conclusions:TGFBI may be useful for the identification of a subset of NSCLC who may benefit from adjuvant therapy.

RETRACTED: Clinical significance of the best response during repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma

We assessed the clinical implications of the best response compared with the initial response during repeated transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We evaluated 332 patients with intermediate-stage HCC and preserved liver function initially treated with repeated TACE. All had ≥1 lesion measuring ≥1 cm, and the response measured after each session was based on EASL and mRECIST criteria. We performed survival analyses according to response kinetics, and identified clinical factors associated with the need for repeated TACE to achieve the best response. An objective response, either a complete response (CR) or a partial response (PR), after the first TACE was seen in about 50% of patients by both EASL and mRECIST. In terms of the best response during serial TACE, 250 patients (75.3%) by EASL and 278 (83.7%) by mRECIST were overall responders. The sizes of the largest and second largest tumors were the only parameters positively correlated with the number of TACE sessions required to achieve the best response (p<0.05). Multivariate Cox analysis showed that achieving a CR or PR as the best response was the best predictor of survival following TACE with a hazard ratio of 0.45 by EASL and 0.24 by mRECIST, and more than 0.69 and 0.71, respectively for initial responders (p<0.05). The best response observed during serial TACE, rather than the initial response, most strongly predicts the survival of patients with intermediate-stage HCC. The number of TACE sessions needed to achieve a best response is a function of tumor size.

Does young age influence the prognosis of colorectal cancer: a population-based analysis.

BackgroundControversy exists whether young patients diagnosed with colorectal cancer have a poorer prognosis. Although younger patients are more likely to have certain poor prognostic factors, prior studies have shown mixed results in terms of overall prognosis, which may be due to lack of adjustment for confounding factors. The primary objective of our study was to determine the effect of age on survival following treatment of colorectal cancer in the Province of Manitoba, Canada, while controlling for important cofactors.MethodsThis was a population-based analysis of all adult patients (age ≥18 years) diagnosed with adenocarcinoma of the colon or rectum between 1 January 2004 and 31 December 2006 in the Province of Manitoba. Patient, tumor, and treatment factors were identified using administrative data. Five-year Kaplan-Meier survival and Cox proportional hazards model were analyzed to determine whether young age (45 years of age or younger) was associated with a poorer prognosis, while controlling for confounding variables.ResultsOf the 2,086 patients identified, 70 (3.36%) were considered young. These patients were more likely to have T4 tumors and node-positive disease. Older patients had more advanced comorbidities. Young age was an independent predictor of better survival. Poorer survival was associated with male gender, increasing stage, higher grade, comorbidity, lower socioeconomic status, and lack of receipt of surgery or chemotherapy.ConclusionsYoung people make up a small minority of patients with colorectal cancer. Young patients present with more locally advanced colorectal cancer. Despite this, on a population basis, their prognosis may be more favorable than their older counterparts when controlling for disease, patient, and treatment factors.

Equity in Ghanaian Breast Cancer Treatment Outcomes-A modeling study in Komfo Anokye Teaching Hospital

To the Editor: In high-income countries, much progress has been made in reducing breast cancer mortality (1,2). However, the benefits of decreased mortality are not distributed equitably, meaning that some subpopulations suffer more from breast cancer than others. Studies have revealed differences in breast cancer burden by race (3), urbanization (4), insurance status (5,6), and socioeconomic status (SES) (7). While equity in breast cancer has been studied in middle-income countries (8,9), it has rarely been examined in low-income countries. This letter reports on the equity of breast cancer treatment outcomes in Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, where we investigated whether lower SES patients present with more advanced disease and have worse health outcomes than other patients. We applied an existing mathematical model to estimate the cost-effectiveness of breast cancer treatments in Ghana (10) using the World Health Organization’s CHOosing Interventions that are Cost Effective (WHO-CHOICE) methodology and WHO population model templates (WHO PopMod) (11). The model included the four disease stages defined by the American Joint Committee on Cancer (12). As breast cancer stage is a good predictor of survival (earlier stages have higher survival rates than later stages (13)), the model uses a patient population’s stage distribution at diagnosis to predict treatment outcomes. Between November 2009 and January 2010, we identified SES and breast cancer stage at diagnosis for 90 patients who had, or were still receiving, treatment in KATH. SES based on expenditures was retrieved using a validated questionnaire, which also contained a question on insurance status (14). Patients were then categorized into SES quintiles, with the first representing the poorest 20% in the population and the fifth quintile representing the richest 20%. We then compared the averted Disability Adjusted Life Years (DALYs) between SES quintiles. The DALY is a summary measure of population health, which represents the sum of the years of life lost due to premature mortality in the population plus the equivalent “healthy” years lost due to nonfatal health conditions (15). DALYs were discounted at an annual rate of 3%. We compared the treatment outcomes of the SES quintiles in terms of DALYs averted with the population not receiving treatment and experiencing the natural progression of the disease.

HLA-G expression is an independent predictor for improved survival in high grade ovarian carcinomas.

Aberrant expression of human leukocyte antigens (HLA) class I has prognostic importance in various cancers. Here, we evaluated the prognostic value of classical (A/B/C) and nonclassical (G/E) HLA expression in 169 high grade epithelial ovarian cancer samples and linked that to clinicopathological characteristics and survival. Expression of HLA-A, -B/C, or -E was not correlated with survival. Survival was prolonged when tumours expressed HLA-G (P = 0.008) and HLA-G was an independent predictor for better survival (P = 0.011). In addition, HLA-G expression was associated with longer progression-free survival (P = 0.036) and response to chemotherapy (P = 0.014). Accordingly, high expression of HLA-G mRNA was associated with prolonged disease-free survival (P = 0.037) in 65 corresponding samples. Elevated serum-soluble HLA-G levels as measured by enzyme-linked immunosorbent assay in 50 matched patients were not correlated to HLA-G protein expression or gene expression nor with survival. During treatment, sHLA-G levels declined (P = 0.038). In conclusion, expression of HLA-G is an independent prognostic factor for improved survival in high grade epithelial ovarian cancer and a predictor for platinum sensitivity.

Within the genome, long telomeres are more informative than short telomeres with respect to fitness components in a long‐lived seabird

Telomeres, DNA-protein structures at chromosome ends, shorten with age, and telomere length has been linked to age-related diseases and survival. In vitro studies revealed that the shortest telomeres trigger cell senescence, but whether the shortest telomeres are also the best biomarker of ageing is not known. We measured telomeres in erythrocytes of wild common terns Sterna hirundo using terminal restriction fragment analysis. This yields a distribution of telomere lengths for each sample, and we investigated how different telomere subpopulations (percentiles) varied in their relation to age and fitness proxies. Longer telomeres within a genome lost more base pairs with age and were better predictors of survival than shorter telomeres. Likewise, fitness proxies such as arrival date at the breeding grounds and reproductive success were best predicted by telomere length at the higher percentiles. Our finding that longer telomeres within a genome predict fitness components better than the shorter telomeres indicates that they are a more informative ageing biomarker. This finding contrasts with the fact that cell senescence is triggered by the shortest telomeres. We suggest that this paradox arises, because longer telomeres lose more base pairs per unit time and thus better reflect the various forms of stress that accelerate telomere shortening, and that telomeres primarily function as biomarker because their shortening reflects cumulative effects of various stressors rather than reflecting telomere-induced cell senescence.