High Prognostic Score Research Articles

Predicting survival with the Heidelberg prognostic model after salvage radiosurgery of previously irradiated progressive high-grade gliomas

The study aimed to determine which patients with previously irradiated progressive high-grade gliomas (PHGG) are likely to benefit from salvage stereotactic radiosurgery (SSRS) using the Heidelberg prognostication model (HPM). Twenty-five study participants with PHGG underwent SSRS between 2000 and 2010. There were 5 and 20 patients with determined low or high HPM prognostic scores, respectively. Overall median survival (MS) was 7 months (range, 1 to 32 months). The 6-, 12- and 24-month crude survival rates (CSR) were 60%, 28% and 16%, respectively. The MS and CSRs for the low-scoring patients were 20 months, 100%, 100% and 20%, respectively; for the 20 individuals with higher scores, the corresponding findings were 8 months, 75%, 35% and 10%, respectively. Among the evaluable 11 patients, the quality of remaining life after therapy was acceptable in approximately half of the cases. Acute and late toxicity were not observed in the retreated subjects. A trend towards improved survival, even if not statistically significant, was observed in the low HPM scoring patients. More documentation of favorable effects from the application of SSRS in people with PHGG is required to support its useful role as a second line treatment.

Clinical significance of prognostic score based on age, tumor size, and grade in gastric cancer after gastrectomy

BackgroundPostoperative management and survival of gastric cancer is mainly determined by pathologic TNM stage. However, gastric cancer is a heterogeneity group, and the survival is quite different even when they are in the same TNM stage. Moreover, TNM stage system does not grasp other important clinicopathologic factors to determine the survival. The aim of the present study is to propose and validate prognostic score based on age, tumor size, and grade.Materials and methodsPatients diagnosed with gastric cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2012 were included in the present study. Kaplan–Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.ResultsA total of 26,091 eligible patients diagnosed with noncardia gastric cancer were included in the study. In the univariate and multivariate survival analysis, age at diagnosis, tumor grade, and tumor size were validated as independent prognostic factors (P<0.05). Then, we proposed a prognostic score calculated from the number of risk factors, with 0, 1, and 2 points each given for favorable, intermediate, and poor prognostic categories of age (≤50, 50–70, and >70), grade (well, moderate, and poor differentiation), and size (≤3, 3–6, ≥7 cm). The prognostic score was verified as independent predictor in both univariate and multivariate survival analyses (P<0.001). In addition, nomograms on cause-specific survival were established according to prognostic factor and all other significant factors, and c-index was 0.715 (95% CI: 0.706–0.725).ConclusionPrognostic score based on age, tumor size, and grade is an independent predictor of survival after gastrectomy. The novel prognostic score can improve the accuracy of prediction for current TNM stage system. Patients who are with a high prognostic score should undergo extensive follow-up after surgery.

A Routine Laboratory Data-Based Model for Predicting Recurrence After Curative Resection of Stage II Colorectal Cancer.

Background: Use of chemotherapy in stage II colorectal cancer (CRC) is controversial because it improves survival only in some patients. We aimed to develop a statistical model using routine and readily available blood tests to predict the prognosis of patients with stage II CRC and to identify which patients are likely to benefit from chemotherapy. Methods: We divided 422 patients with stage II CRC into a training and a testing set. The association of routine laboratory variables and disease-free survival (DFS) was analyzed. A prognostic model was developed incorporating clinically relevant laboratory variables with demographic and tumor characteristics. A prognostic score was derived by calculating the sum of each variable weighted by its regression coefficient in the model. Model performance was evaluated by constructing receiver operating characteristic curves and calculating the area under the curve (AUC). Results: Significant associations were seen between 5 laboratory variables and patient DFS in univariate analyses. After stepwise selection, 3 variables (carcinoembryonic antigen, hemoglobin, creatinine) were retained in the multivariate model with an AUC of 0.75. Compared with patients with a low prognostic score, those with a medium and high prognostic score had a 1.99- and 4.78-fold increased risk of recurrence, respectively. The results from the training set were validated in the testing set. Moreover, chemotherapy significantly improved DFS in high-risk patients, but not in low- and medium-risk patients. Conclusions: A routine laboratory variable-based model may help predict DFS of patients with stage II CRC and identify high-risk patients more likely to benefit from chemotherapy.

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy.

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had ≥3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies.

Cell-Free Circulating Epigenomic Signatures: Non-Invasive Biomarker for Cardiovascular and Other Age-Related Chronic Diseases.

The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.

Genomic profile in gestational and non-gestational choriocarcinomas

IntroductionGestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases. MethodsThirteen patients were included in this study; 10 presented previous history of hydatidiform mole and six developed metastasis. Twelve polymorphic microsatellite markers (D15S659, APOC2, D5S816, BAT25, D3S1614, D3S1311, D1S1656, APC-D5S346, D3S1601, D18S70, D8S1110 and D11S1999) were investigated to distinguish GC from NGC. All choriocarcinomas were evaluated by copy number alterations using array CGH. ResultsEight cases were classified as GC and five as NGC. Although potentially polymorphic, NGC exhibited significant gain of 21p11. Rare copy number alterations (CNA) were detected as a frequent event in GC including gains of 1p36.33-p36.32 (3 cases), 17q25.3 (4 cases), and losses of 9q33.1 (5 cases), 17q21.3 (3 cases) and 18q22.1 (4 cases) (varying from 724 to 3,053 Kb). DiscussionTwo tumor suppressor genes are candidates to be involved in GC: TRIM32 (9q33.1) and CDH19 (18q22.1). Gains of CBX2, CBX4 and CBX8 were frequently found in high risk prognostic score in GC. The in silico functional interaction analysis revealed the involvement of PTEN and PI3K-Akt signaling pathways. These data pointed out significant genomic alterations in GC, opening new avenues to better characterize the pathobiology of this disease.

Symptom Burden As Primary Driver for Therapy in Patients with Myelofibrosis: An Analysis By MPN International Quality of Life Study Group

Symptom Burden As Primary Driver for Therapy in Patients with Myelofibrosis: An Analysis By MPN International Quality of Life Study Group

Prognostic Factors and a New Prognostic Index Model for Children and Adolescents with Hodgkin's Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation: A Multicenter Study of the Turkish Pediatric Bone Marrow Transplantation Study Group.

Objective:The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin’s lymphoma (HL) were evaluated.Materials and Methods:The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis.Results:The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival.Conclusion:The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis.

TAS-102 versus placebo plus best supportive care in patients with metastatic colorectal cancer refractory to standard therapies: Final survival results of the phase III RECOURSE trial.

634 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial. Original results of RECOURSE based on the cut-off date of January 24, 2014, in which 72% of mortality events had occurred, demonstrated a significant improvement in overall survival (OS) with TAS-102 vs placebo. Here we report results of an updated survival analysis from RECOURSE and a retrospective analysis of OS outcomes based on a clinical prognostic risk index. Methods: Patients were randomized 2:1 to receive TAS-102 or placebo. Study treatment continued until disease progression, death, or unacceptable toxicity. The primary endpoint was OS; final survival data were collected on October 8, 2014. A clinical OS prognostic risk score was assessed to evaluate OS effect in patients from low to high prognostic score. Prognostic factors contributing to the risk index were from those prespecified in the multivariate modeling assessment of OS outcome. Results: At data cut-off for the final survival analysis, 89% of the 800 patients randomly assigned to TAS-102 or placebo had died, accounting for 138 events in addition to 574 (72%) events included in the original analysis. The updated results for OS are shown in the Table. Conclusions: An updated survival analysis confirmed that OS benefit with TAS-102 was maintained and increased to a full 2 months; improvement in 1-year survival surpassed 10% in these heavily pretreated patients. OS benefit appears to be maintained for all patients in the trial regardless of prognostic status at trial entry. Clinical trial information: NCT01607957. [Table: see text]

Patient-Reported Outcomes in Myelofibrosis Patients Help to Identify Patients' Needs

Myelofibrosis (MF) is the most symptomatic of the myeloproliferative neoplasms and is associated with the greatest symptom burden and poorest prognosis. Patient-reported outcomes is an effective way to identify patients' needs and risks/benefits of MF treatment. We aimed to study quality of life (QoL) and symptom burden in MF patients in a real-world setting.44 MF patients - 27 primary MF, 8 post-essential thrombocytopenia, 9 post-polycythemia vera - were enrolled in the multicenter real-world QoL study. Mean age - 60.8±13.3; male/female - 14/30. All the patients received the best available treatment (BAT, n=28) or novel treatment modality ruxolitinib (n=16) for at least 6 months (range 6-160 mths). A high proportion of patients (80%) had intermediate to high prognostic risk scores according to International Prognostic Scoring System. All the patients completed the QoL questionnaire SF-36, symptom assessment questionnaire CSP-MF and Patient Global Impression of Change (PGIC) tool. Integral QoL Index (IQoLI) in MF patients was calculated on the basis of SF-36 and QoL impairment grade was assessed in comparing with QoL population norms (PN). Comparison t-test for independent samples or Mann-Whitney test was applied.The heterogeneity of MF patients population in terms of QoL impairment was shown: 55% of patients had mild QoL impairment (IQoLI≤25% from PN), 7% - moderate (IQoLI≤25-50% from PN), 38% - severe or critical QoL impairment (IQoLI≤50% from PN). Patients receiving BAT exhibited more pronounced QoL impairment as compared to patients receiving ruxolitinib (p<0.05); they had worse physical functioning, general health, vitality, social functioning, and mental health (p<0.05). All the patients experienced multiple symptoms; the most severe symptoms were fatigue, inactivity and pain in bones/muscles. The symptoms were more expressed in patients on BAT as compared to patients on ruxolitinib (p<0.005). Patient's impression of health changes was better in patients treated with ruxolitinib: the mean PGIC score was higher in patients on BAT on ruxolitinib - 4.4 vs 2.3 (p=0.001).Quality of life and perceived change in health condition are better and symptom severity is less in MF patients on ruxolitinib therapy than those on BAT. Results of this real-world study demonstrate benefits of ruxolitinib therapy from patient perspective. Patient-reported outcomes are of help to better identify the needs of MF patients. DisclosuresNo relevant conflicts of interest to declare.

Nutritional risk assessment in critically ill cancer patients: systematic review.

ObjectiveTo systematically review the main methods for nutritional risk assessment used in critically ill cancer patients and present the methods that better assess risks and predict relevant clinical outcomes in this group of patients, as well as to discuss the pros and cons of these methods according to the current literature.MethodsThe study consisted of a systematic review based on analysis of manuscripts retrieved from the PubMed, LILACS and SciELO databases by searching for the key words “nutritional risk assessment”, “critically ill” and “cancer”.ResultsOnly 6 (17.7%) of 34 initially retrieved papers met the inclusion criteria and were selected for the review. The main outcomes of these studies were that resting energy expenditure was associated with undernourishment and overfeeding. The high Patient-Generated Subjective Global Assessment score was significantly associated with low food intake, weight loss and malnutrition. In terms of biochemical markers, higher levels of creatinine, albumin and urea were significantly associated with lower mortality. The worst survival was found for patients with worse Eastern Cooperative Oncologic Group - performance status, high Glasgow Prognostic Score, low albumin, high Patient-Generated Subjective Global Assessment score and high alkaline phosphatase levels. Geriatric Nutritional Risk Index values < 87 were significantly associated with mortality. A high Prognostic Inflammatory and Nutritional Index score was associated with abnormal nutritional status in critically ill cancer patients. Among the reviewed studies that examined weight and body mass index alone, no significant clinical outcome was found.ConclusionNone of the methods reviewed helped to define risk among these patients. Therefore, assessment by a combination of weight loss and serum measurements, preferably in combination with other methods using scores such as Eastern Cooperative Oncologic Group - performance status, Glasgow Prognostic Score and Patient-Generated Subjective Global Assessment, is suggested given that their use is simple, feasible and useful in such cases.

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

Introduction:The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality.Methods:Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome.Results:The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7).Conclusions:This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality.

Retrospective analysis of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) as salvage chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer: inflammation-based prognostic score predicts survival.

The purpose of this study was to assess the efficacy and safety of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) in patients with gemcitabine (GEM)-refractory pancreatic cancer (PC) and to explore independent variables associated with survival. We retrospectively reviewed consecutive patients with GEM-refractory PC who received FGS at our institution from March 2009 to December 2013. GEM was administered by fixed dose rate intravenous infusion of 1,200mg/m(2) as a 120-min infusion on day 1, and S-1 was administered orally twice a day at a dose of 40mg/m(2) on days 1-7. Cycles were repeated every 14days. Sixty-one patients with GEM-refractory PC received FGS. Sixteen patients received FGS as third-line treatment. Twenty-nine patients (48%) had a history of S-1 administration. The objective response rate was 13%, and the disease control rate was 49%. The median progression-free survival time was 2.7months, and the median overall survival time was 6.0months. Major Grade 3 or 4 adverse events included neutropenia (15%), diarrhea (3%), anorexia (2%), and fatigue (2%). A high inflammation-based prognostic score (modified Glasgow prognostic score (mGPS), which incorporates C-reactive protein and albumin), a performance status >0, and serum carbohydrate antigen 19-9 level >2,000IU/ml were independently associated with a poor outcome. FGS might be effective and well tolerated as salvage chemotherapy in a practical setting. The inflammation-based prognostic score is a simple and reliable indicator of survival in the setting of salvage chemotherapy.

Long Term Results of a Multicenter Prospective Trial By the Lysa Group Evaluating the RiPAD+C Regimen (Combination of Rituximab, Bortezomib, Doxorubicin, Dexamethasone and Chlorambucil) As First-Line Therapy for Elderly Mantle Cell Lymphoma Patients (MCL): Prognostic Value of FDG-PET/CT

Background:Mantle cell lymphoma (MCL) is an aggressive lymphoma with variable 18Fluorine-Deoxyglucose (FDG) avidity. FDG - Positron Emission Tomography/Computed Tomography (FDG-PET/CT) is not yet recommended in MCL but many retrospective studies have underlined its prognostic impact either before any treatment or at interim or final time points of R-chemotherapy. The French LYSA/GOELAMS group published the results of a multicenter prospective phase II clinical trial evaluating the RiPAD + C front-line combination including one proteasome inhibitor (PS341-Velcade®) for elderly MCL patients(Houot, Le Gouill et al. 2012). The aim of the present study was to determine the prognostic value of FDG-PET/CT in this prospective cohort with a long follow up.Method:Patients between 65 and 80 years old were enrolled. They received 4 cycles of RiPAD+C regimen (every 35 days: Rituximab 375 mg/sqm D1, Velcade® 1.3 mg/sqm D1,4,8 and 11, Doxorubicin 9 mg/sqm D1 to D4, Dexamethasone 40 mg D1 to 4 and Chlorambucil 12 md D20 to D29) and 2 additional cyclesif they responded (IWR criteria). Three FDG-PET scans were performed: an initial pre-treatment, after 4 cycles (interim) and after 6 cycles (post-treatment). All available FDG-PET/CT were centrally reviewed by two experts, using visual international response assessment criteria proposed by IHP in Lymphoma and the Deauville five-point scale. The maximal standardized uptake value (SUVmax) and maximal standardized uptake value reduction (ΔSUVmax) of the most intense pathological area were measured.Results:From June 2007 to December 2008, 39 patients from 21 French centers were recruited. After 64 months follow-up for the 22 surviving patients, median overall survival (OS) has not been reached (the 3 year OS was 63,5%). Median progression free survival (PFS) is 22 months. Seventeen patients died either from lymphoma (n=13) or due to toxicity (n=4).Seventy-eight FDG-PET/CT were performed (31 initial FDG-PET/CT; 28 interim, 19 post-treatment), in 39 patients. We reviewed 24 initial FDG-PET/CT, 27 interim, and 16 post-treatment. By univariate analysis: neither initial, interim nor post-treatment FDG-PET/CT were predictive of OS or PFS. The ΔSUVmax (> 65% vs ≤ 65%, or > 50% vs ≤ 50%) was also not predictive for OS or PFS (p= 0.48 to 0.92). However high SUVmax (>10 vs ≤10) and clinical prognostic scores (MIPI or the Goelams index) correlated with OS (p=0.09, p= 0.054 and p=0.16, respectively). In a multivariate analysis patients with a high prognostic score at diagnosis combined with a positive post-treatment FDG-PET/CT had very poor OS compared to other profiles (high index with a negative post-treatment FDG-PET/CT or low-intermediate index with a negative or positive FDG-PET/CT).Conclusion:This is the first prospective study evaluating the prognostic impact of FDG-PET/CT in a cohort of homogeneously treated MCL patients with a long time of follow up. Neither initial, interim or post-treatment FDG-PET/CT were predictive of PFS or OS. However we confirm, as previously described in a retrospective analysis (Bodet-Milin, Touzeau et al. 2010), that both high SUVmax at initial FDG-PET/CT and the MIPI score were prognostic for OS. Interestingly, a negative post-treatment FDG-PET/CT seemed to erase the adverse prognostic significance of a high MIPI score before treatment. These observations warrant further confirmation in large prospective clinical trials. DisclosuresLe Gouill:Roche: Consultancy; Janssen: Consultancy. Dartigeas:Roche: Consultancy. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Gressin:MundiPharma: Other.

Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States

Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs).Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores.Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (>98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was >2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%).Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. [Display omitted] DisclosuresMesa:Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity’s Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity’s Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

Anastomotic Leaks after Colorectal Surgery: a Prognostic Score

Abstract Introduction: Anastomotic leaks are one of the most dreaded complications in colorectal surgery. At the ground of this problem remain the nefarious prognostic over the patient’s life, the difficulties in early diagnosis and the optimal choice of therapeutical methods. The goal of our research was to evaluate the significance of possible risk factors in the postoperative evolution of patients following colorectal interventions and to design a prognostic score. Material and methods: We performed a retrospective study on 298 cases of patients with inflammatory, neoplastic or traumatic lesions for which there was chosen a digestive anastomosis including the colon. The presumed risk factors in our analysis were: age, comorbidity evaluated by Charlson Score, etiology, toxics, use of nonsteroidal anti-inflammatory substances or corticoids, parameters such as leucocytes, hemoglobin, urea, total seric bilirubin, glycaemia, albumins, neoadjuvant therapy, type of suture, quantity of fluids received intraoperatory. All data were analyzed using R-Commander. Results: All parameters for which we demonstrated a statistical significance (p &lt;0.05) for an unfavorable evolution were included in a prognostic score, designed in correlation with the statistical relation between the factors. We obtained values that certified a strong association (0.75) between a high prognostic score and an increased number of anastomotic leaks. Conclusions: The practical utility of the score is mainly for the anticipation of postoperative complications. A high level score underlines that prior to surgery it is essential to balance the biochemical abnormalities and to choose properly the moment and type of surgical intervention

A revised scope in different prognostic models in cirrhotic patients: Current and future perspectives, an Egyptian experience

Background and study aimThe prognosis of cirrhosis is of great interest for liver transplantation and new therapies of related complications. Traditional prognostic models such as Child–Pugh (CP) and Model for End-stage Liver Disease (MELD) were developed to predict mortality in decompensated cirrhosis, but lack parameter(s) related to complications. Recently, new models such as creatinine-modified Child–Turcotte–Pugh (CrCTP) and sodium-based MELD variants were developed to improve prognostic accuracy and enhance outcome predictive capability. Our aim was to investigate the prognostic ability of these models and their relation to complications among Egyptian cirrhotic patients to determine the best one and to assess adding new variables to improve the prognostic ability of that model. Patients and methodsA total of 1000 cirrhotic patients were enrolled in a retrospective study; traditional and new prognostic models such as CP, MELD, CrCTP, integrated MELD (iMELD), MELD plus sodium (MELD-Na, MELDNa) and MELD:sodium ratio (MESO) were calculated. The predictive abilities of prognostic models were compared using the area under receiver operating characteristic curve (AUC) and 1-year survival rates were evaluated by Kaplan–Meier survival analysis. An index of cirrhosis-related complications was added to reveal the best prognostic model. ResultsUsing AUC, MELD and its sodium variants was significantly better than CP and CrCTP scores in predicting risk of 1-year mortality, where MELD-sodium (MELD-Na) had the highest AUC (0.743). Adding an index of cirrhosis-related complications (C) to MELD-Na creating a new scoring system (MELD-Na-C) improved its prognostic accuracy (AUC 0.753). Kaplan–Meier survival curves predicted increased mortality with higher prognostic scores. ConclusionsAll prognostic models were good predictors of 1-year mortality in patients with decompensated cirrhosis; however, MELD-Na was the best for outcome prediction. MELD-Na-C was a new model enhancing the predictive accuracy in assessing cirrhotic patients with related complications.

Invasive properties of papillary thyroid cancer with concurrent BRAF(V600E) mutation and rearranged during transfection proto-oncogene protein expression

To investigate the aggressive properties of papillary thyroid cancer (PTC) with concurrent BRAF(V600E) mutation and rearranged during transfection (RET) proto-oncogene protein expression. Fifty pathologically confirmed PTC patients who had received thyroidectomy were enrolled in this study. BRAF(V600E) mutation was detected by real time polymerase chain reaction (RT-PCR), while RET protein expression was measured by immunohistochemical SP method. Clinical and pathological features were compared between the concurrent BRAF(V600E) mutation and RET protein expression group (n=24) and BRAF(V600E) mutation or RET protein expression alone group (n=19). Seven patients were ruled out from the final analysis due to the absence of either BRAF(V600E) mutation or RET protein expression. Of these 50 patients, BRAF(V600E) mutation and RET protein expression were detected in 38 patients (76%) and 28 patients (56%), respectively. Concurrent BRAF(V600E) mutation and RET expression was detected in 24 patients (48%). Compared with the concurrent BRAF(V600E) mutation and RET protein expression group, the BRAF(V600E) mutation or RET protein expression alone group had relatively poorer tissue differentiation and higher prognostic score (P=0.011, P=0.022). PTC patients with concurrent BRAF(V600E) mutation and RET expression present poorer differentiation, more highly aggressive variant in carcinoma tissues, and higher cancer-related mortality risk.

Azacitidine‐eligibility in higher‐risk myelodysplastic syndromes and chronic myelomonocytic leukaemia: a registry‐based study

Azacitidine‐eligibility in higher‐risk myelodysplastic syndromes and chronic myelomonocytic leukaemia: a registry‐based study

Cumulative Number of Altered Biomarkers in Mammalian Target of Rapamycin Pathway Is an Independent Predictor of Outcome in Patients With Clear Cell Renal Cell Carcinoma

To evaluate the association of the altered expression of the mammalian target of rapamycin (mTOR) pathway components with oncologic outcomes in patients with nonmetastatic clear cell renal cell carcinoma (ccRCC). Immunohistochemistry for phosphorylated-S6, phosphorylated-mTOR, mTOR, phosphorylated-AKT, hypoxia inducible factor-1α, Raptor, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and phosphorylated 4E-binding protein-1 was performed on tissue microarray constructs of patients treated for nonmetastatic kidney cancer from 1997 to 2010. The relationship between individual altered marker expression and a prognostic marker score (low, intermediate, and high, defined as ≤ 3, 4-5, >5 altered biomarkers, respectively) and oncologic outcome was assessed. The study included 419 patients with nonmetastatic ccRCC, with a median follow-up period of 26 months (range 6-150). The tumors were nonorgan confined (pT3-T4) in 86 (20.5%) and high Fuhrman nuclear grade (3-4) in 131 (31%). A low, intermediate, and high prognostic marker score was found in 214 (51%), 152 (36%), and 53 (13%) patients, respectively. Kaplan-Meier analysis demonstrated a statistically significant correlation between the risk groups and disease recurrence and cancer-specific survival. In a multivariate Cox regression analysis controlling for tumor stage and grade, a high marker score was an independent predictor of disease recurrence (hazard ratio 3.3, 95% confidence interval 1.33-8.39, P = .01), and a combination of a high and an intermediate score was an independent predictor of survival (hazard ratio 4.8, 95% confidence interval 1.27-4.78, P = .008). The cumulative number of aberrantly expressed biomarkers correlated with aggressive tumor biology and inferior oncologic outcomes in patients with ccRCC. Our data support prospective pathway-based exploration of the mTOR signaling cascade to augment current clinicopathologic predictors of oncologic outcomes in patients with ccRCC.