Prognostic Factor For Clinical Outcome Research Articles

Prognostic factors for clinical outcomes in patients with metastatic castration resistant prostate cancer treated with sequential novel androgen receptor-directed therapies.

Prognostic factors associated with clinical outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with a novel androgen receptor-directed therapies (ARDT) in the second line setting has not been formally evaluated. We retrospectively reviewed and analyzed medical records of all patients with mCRPC who received sequential treatment with ARDT. We analyzed potential clinical factors associated with post treatment endpoints including 50% decline in prostatic-specific antigen (PSA), PSA-progression-free survival (PFS), clinical or radiographic PFS and overall survival (OS). Prognostic univariate and multivariate Cox proportional hazard models were developed and assessed. One hundred twenty-six patients with mCRPC treated with a second-line novel ARDT were included. Overall, 50% decline in PSA was observed in 22% of patients and a median PSA-PFS of 2.9 months and a PFS of 3.6 months. After adjusting for potential confounders including prior exposure to docetaxel and number of prior antiandrogen agents, time to development of CRPC was an independent factor associated with PSA-PFS (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.99-1; P = 0.02) and PFS (HR: 0.99; CI: 0.98-1; P= 0.01). PSA response (50% decline) to first-line novel ARDT correlated negatively with PSA-PFS with second-line novel ARDT (HR: 1.7; 95% CI: 1.14-2.53; P = 0.009) and lower pre-treatment levels of albumin were associated with shorter PFS (HR: 0.56; 95% CI: 0.32-0.97; P = 0.03). Performance status, pre-treatment levels of albumin, extent of disease and time to development CRPC were associated with OS. Second-line ARDT is associated with modest outcomes in patients with mCRPC. Time to development of CRPC is the strongest predictor of PSA response, PSA-PFS and OS which suggest that intrinsic resistance to AR directed treatment is the major treatment outcome factor in these patients. Future studies in patients receiving long term ARTD should include the identification of predictive biomarkers to facilitate treatment selection.

Prognostic Factors for Clinical Outcomes in Autotransplantation of Teeth with Complete Root Formation: Survival Analysis for up to 12 Years

IntroductionTooth autotransplantation is a treatment option that has the potential to restore masticatory function and esthetics to edentulous spaces resulting from extracted teeth. The purpose of this study was to investigate the prognostic factors and clinical outcomes for autotransplanted teeth with complete root formation. MethodsPatients who had received tooth autotransplantation in the Department of Conservative Dentistry, Yonsei University Dental Hospital, Seoul, Korea, from July 2001 to August 2010 were electronically searched, and a total of 105 cases of autotransplanted teeth met the inclusion criteria. Tooth survival, inflammatory root resorption (IRR), ankylosis, and related prognostic factors were assessed by using the survival analysis that was based on clinical and radiographic examination. ResultsThe cumulative tooth survival rate was 68.2% at 12 years after the tooth autotransplantation. According to the Cox proportional hazard regression analysis, patient age, donor position, and extraoral time were significantly associated with tooth survival (P < .05). Donor extraction type was significantly associated with IRR (P < .05), and transplantation timing and initial stability were significantly associated with ankylosis (P < .05) ConclusionsPatients less than 45 years of age, maxillary donor teeth, and an extraoral time of less than 15 minutes were associated with significantly higher tooth survival. Surgical extraction of the donor tooth was associated with a significantly higher incidence of IRR. Immediate transplantation after the extraction of the recipient site's tooth and low initial stability were associated with a significantly lower incidence of ankylosis

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke.

BackgroundEndovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.MethodsWe conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.ResultsEighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.ConclusionMultiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.

Lymphocyte-to-Monocyte Ratio at Diagnosis and Survival in De Novo Double/Triple Hit Diffuse Large B-Cell Lymphoma

The lymphocyte-to-monocyte ratio at diagnosis (LMR-D) has been reported to be a prognostic factor for clinical outcomes in both T-cell and B-cell lymphomas. However, there are no reports testing the prognostic ability of LMR-D in patients diagnosed with de novo double/triple hit diffuse large B cell lymphoma (DLBCL). Thus, we set out to investigate if the LMR-D is a prognostic factor for survival in de novo double/triple hit lymphomas. From 10/5/1998 until 1/16/2015, thirty-four patients with de novo double/triple hit DLBCL were identified for this study. Double and triple hit were defined by interphase FISH evaluating three fusion signals to identify the BCL2 translocation and IGK/MYC D-FISH probe to identify whether the partner is IG or non-IG. Interphase fluorescence in situ hybridization (FISH) was performed on paraffin sections using probes that included 8q24 (5'MYC, 3'MYC); t (2;8), IGK/MYC; t(8,14), MYC/IGH; t(8;22), MYC/IGL; 3q27 (3'BCL6, 5'BCL'6); and 18q21 (3'BCL2, 5'BCL2). The cohort included 14 females and 20 males. The median follow-up for the cohort was 9.0 months (range: 0.4-72.6 months). Using the median for the LMR-D as the cut-off value, patients with a LMR-D ≥ 1.2 experienced superior overall survival (OS) [Hazard ratio (HR) of 0.127, 95% confidence interval (CI) of 0.019-0.530, p < 0.004] and progression-free survival (PFS) [HR of 0.107, 95 CI of 0.024-0.335, p < 0.0001]. The median follow up for OS for patients with a LMR-D ≥ 1.2 was not reached with a 5-year OS rate of 82% (95% CI of 49%-95%) compared with a median follow-up of 10 months for patients with a LMR-D < 1.2 with a 0% 5 year OS rate, p < 0.003 (Figure 1A). The median PFS for patients with a LMR-D ≥ 2 was not reached with a 5 years PFS of 74% (95%CI, of 43%-91%) compared with a median follow-up of 4.7 months for patients with a LMR-D < 1.2 and 0% 5 year PFS rate, p < 0.0001 (Figure 1B). After adjusting for the International Prognostic Index, multivariate analysis showed that the LMR-D remained an independent prognostic factor for OS [HR = 0.180, 95% CI of 0.254-0.784, p < 0.02] and for PFS [HR of 0.127, 95%CI of 0.029-0.409, p < 0.0003]. In spite of the small cohort of de novo double/triple hit DLBCL, the LMR-D was identified as a prognostic factor for clinical outcomes for this specific set of aggressive lymphomas. Further studies are warranted to confirm our findings. TableLMR-D ≥ 1.2, N = 18Events = 2LMR-D < 1.2, N = 16Events = 8P < 0.003LMR-D ≥ 1.2, N = 18Events = 3LMR-D < 1.2, N = 16Events = 14P < 0.0001Figure 1AB [Display omitted] DisclosuresMaurer:Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Off Label Use: New agent in a combination regimen..

PET-Based Textural Analysis Assessment in Early Stage Hodgkin Lymphoma Treated with Standard Combined Approach

BACKGROUNDInterim 18F-fluorodeoxyglucose positron tomography (PET) has been shown to be a prognostic factor for clinical outcome in Hodgkin lymphoma (HL). Predicting an early cancer's response to chemotherapy could enhance clinical care management by enabling the personalization of treatment plans based on predicted outcome. Tumour texture can be measured from medical images that provide a non-invasive method of capturing intratumoral heterogeneity and hence could potentially allow a prior assessment of a patient's predicted response to treatment.PURPOSEThe aim of the study was to assess the applicability of the pre-treatment PET-based textural analysis (TA) in a cohort of early stage HL and its correlation with early response to chemotherapy.METHODSWe reviewed medical records of patients with early stage HL diagnosed between January 2012 and December 2014 treated with standard combined modality therapy. All PET scans were reviewed by a local nuclear medicine physician, blinded for the clinical outcome and interim PET (iPET) results. TA was applied to pre-treatment PET images in order to extract features which can be used as prognostic factors for early treatment response. TA features provide unique information about the spatial variation of pixels in the segmented Volume of Interests (VOIs) where it is applied thus they are able to quantitatively score tumor heterogeneity. In order to do this, two different strategies were employed. First was to segment pathological lymph nodes with a 40% of SUVmax isocontour algorithm. Each lymphnode was analysed with TA as a "stand-alone patient" in order to increase the number of observations. Second strategy was to extract two cubes of 3 and 4 cm3 of volume from the highest metabolically active mediastinic region. Seventy-four textural features were calculated mathematically and then analyzed with statistical non parametric test (Kruskall Wallis test). Features which showed prognostic power (or patient stratification ability) were employed to build Receiver Operating Curve (ROC) in order to score their sensibility and specificity.RESULTSTwenty-four patients were selected. After iPET revision, 17 patients were considered disease free after 2 cycles of ABVD whereas the remaining 7 patients had a positive iPET. Considering each lymph node as a "stand-alone patient" we were able to analyse 84 cases.The Kruskall Wallis test showed that 5 out of 74 TA features could separate iPET responders and non-responders patients with statistical significance (p<0.01). Among these 5 features (40% SUVmax segmentation algorithm applied on captant lymph nodes), "coarseness feature" (a feature that scores the granularity of lymph node activity) is able to provide a good discrimination (p<0.005) between iPET responders and non-responders, with an efficiency of 73% (77% sensitivity, 70% specificity). This means that lymph nodes which appear coarser in pre-treatment PET images have a higher probability of being positive at iPET. Results obtained employing the second technique showed that 4 features are able to predict iPET response with statistical significance (p<0.02) but with an even better discrimination efficiency up to 85% employing "uniformity feature" as prognostic factor as can be seen in Fig. 1 and Fig. 2.CONCLUSIONTextural biomarkers as an intratumoral heterogeneity quantification tool hold great promise for the early prediction of tumor outcomes. In this work, we demonstrated the applicability of the PET-based TA in a cohort of cases with early HL. This method requires further validation in a larger prospective study. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic value of Ki-67 in solid pseudopapillary tumor of the pancreas: Huashan experience and systematic review of the literature

Solid pseudopapillary tumor of the pancreas (SPTP) is considered to have a low Ki-67 proliferation index, which may explain the generally good clinical outcome. The aim of our study was to evaluate whether Ki-67 has prognostic value in SPTP. A case series study of patients with SPTP treated in our institution from June 2002 to April 2014 was conducted. Prognostic factors for clinical outcomes were analyzed by the use of clinical decision and survival analysis. In addition, we performed a systematic review and pooled analysis to evaluate our results. The institutional data included 71 patients (13 male and 58 female) ranging in age from 12 to 64 years (median, 31 years). Three patients developed local recurrence and/or liver metastasis after initial surgery. The 5-year recurrence-free survival rate was 93.6%. One patient died of disease, with the 5-year disease-specific survival rate of 98.5%. Ki-67 index ≥ 4% was found significantly associated with the survival of SPTP. Twenty-six studies comprising 163 patients were included in the pooled analysis based on our inclusion criteria. A total of 15 cases showed a Ki-67 index ≥ 4%. Kaplan-Meier survival analysis confirmed that Ki-67 index ≥ 4% was significantly associated with poorer recurrence-free survival and disease-specific survival (both P < .001). This study highlighted a potential role of Ki-67 in predicting adverse outcome of patients with SPTP and should be considered as part of routine histological reporting of SPTP.

Factors Associated with Short-Term Mortality After Surgical Oncologic Emergencies.

BackgroundThe clinical outcome of patients with oncologic emergencies is often poor and mortality is high. It is important to determine which patients may benefit from invasive treatment, and for whom conservative treatment and/or palliative care would be appropriate. In this study, prognostic factors for clinical outcome are identified in order to facilitate the decision-making process for patients with surgical oncologic emergencies.MethodsThis was a prospective registration study for patients over 18 years of age, who were consulted for surgical oncologic emergencies between November 2013 and April 2014. Multiple variables were registered upon emergency consultation, and the follow-up period was 90 days. Multivariate logistic regression analysis was performed to identify factors associated with 30- and 90-day mortality.ResultsDuring the study period, 207 patients experienced surgical oncologic emergencies—101 (48.8 %) men and 106 (51.2 %) women, with a median age of 64 years (range 19–92). The 30-day mortality was 12.6 % and 90-day mortality was 21.7 %. Factors significantly associated with 30-day mortality were palliative intent of cancer treatment prior to emergency consultation (p = 0.006), Eastern Cooperative Oncology Group performance score (ECOG-PS) >0 (p for trend: p = 0.03), and raised lactate dehydrogenase (LDH) (p < 0.001). Additional factors associated with 90-day mortality were low handgrip strength (HGS) (p = 0.01) and low albumin (p = 0.002).ConclusionsDefining the intent of prior cancer treatment and the ECOG-PS are of prognostic value when deciding on treatment for patients with surgical oncologic emergencies. Additional measurements of HGS, LDH, and albumin levels can serve as objective parameters to support the clinical assessment of individual prognosis.

Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: A systematic review and meta-analysis.

The immune system plays an important role in cancer pathogenesis. A low lymphocyte-to-monocyte ratio (LMR), as a simple biomarker of host immune system, has been suggested to be related to poor prognosis in various cancers. We performed a systematic review and meta-analysis to quantify the prognostic value of LMR on clinical outcomes in non-hematologic solid tumors. We searched PubMed and the ASCO online database of meeting abstracts up to July 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment LMR on clinical outcomes in patients with non-hematologic solid tumors. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. A total of 11,197 patients from 29 studies were included. LMR lower than the cut-off was associated with poor OS (HR, 1.73; 95% CI, 1.55-1.93; P<0.001), CCS (HR, 1.56; 95% CI, 1.27-1.91; P<0.001) and DFS (HR, 1.56; 95% CI, 1.31-1.86; P<0.001). The effect of LMR on OS was observed in among various tumor types and across disease stages. The median cut-off value for LMR was 3.0 (range=2.0-5.3). Subgroup analysis according to cut-off value (<3.0, 3.0 to <4.0, 4.0 to <5.0, and ≧5.0) showed a significant prognostic value of LMR on OS in all subgroups. A low pre-treatment LMR seems to represent an unfavorable and robust prognostic factor for clinical outcomes in patients with non-hematologic malignancies. None.

TCT-181 Uric acid is neither the risk factor nor prognostic factor for clinical outcomes during 3-year follow-up period in coronary vasospastic angina

TCT-181 Uric acid is neither the risk factor nor prognostic factor for clinical outcomes during 3-year follow-up period in coronary vasospastic angina

Serbia

Hemorrhage volume, level of consciousness and ventricular extension and expansion of the hematoma are prognostic factors for clinical outcome of intracerebral hemorrhage (ICH). Volumetric measurement of ICH has an important clinical and prognostic meaning. The aim of this study was to compare the methods which are being used to measure ICH volume: the ABC/2 method and semiautomated method with computer volumetric program. Our study represents a retrospective analisys of 54 patients (61.11% male and 38.89% female patients with mean age 67.20±10.30 years) who underwent computed tomography (CT) scan of endocranium. Volumetric measurements were performed by ABC/2 method and computer semiautomated method with volumetric program on Аdvantage Windows 3D Workstation 4.1. Mean value and standard deviation obtained by ABC/2 method were 41.98±35.47, while mean value and standard deviation obtained by computer semiautomated method with volumetric program were 52.12±45.61. There is a statistically significant difference between the values obtained by these two methods (p=0.03). The absolute difference was 10.14 cm. The values acquired by computer method were by 19.46% higher than those acquired by formula. There is a statstically strong positive correlation between these two methods (r=0.852, p<0.05). Both methods are very useful in determining ICH volume. Our results show that values obtained by computer semiauthomatic method were by 19.46% higher than those obtained by the elliptic equation. Elliptic equation-ABC/2 method is better for measuring regular ICH shapes and fast orientation, while semiautomated computer method is more accurate and more selective. Acta Medica Medianae 2015;54(3):34-38.

Prognostic Factors in Hospitalization for Heart Failure in Asia.

The hospitalized heart failure (HF) population is becoming a significant economic burden to Asian countries because of the growing elderly population, increased prevalence of HF, and recurrent rehospitalization. A targeted treatment strategy is needed with prognostic factors that can reduce mortality or rehospitalization after discharge. The accepted prognostic factors include age, low systolic blood pressure, ischemic heart disease, reduced left ventricular function, hyponatremia, and renal dysfunction. Prognostic factors for clinical outcomes in hospitalized patients with HF may be different in Asian people. Further research leading to better understanding of the characteristics of Asian patients hospitalized with HF is warranted.

Infused autograft lymphocyte-to-monocyte ratio and survival in T-cell lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

BackgroundThe infused autograft lymphocyte-to-monocyte ratio (A-LMR) is a prognostic factor for survival in B-cell lymphomas post-autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if the A-LMR is also a prognostic factor for survival post-APHSCT in T-cell lymphomas.MethodsFrom 1998 to 2014, 109 T-cell lymphoma patients that underwent APHSCT were studied. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to identify the optimal cut-off value of A-LMR for survival analysis and k-fold cross-validation model to validate the A-LMR cut-off value. Univariate and multivariate Cox proportional hazard models were used to assess the prognostic discriminator power of A-LMR.ResultsROC and AUC identified an A-LMR ≥ 1 as the best cut-off value and was validated by k-fold cross-validation. Multivariate analysis showed A-LMR to be an independent prognostic factor for overall survival (OS) and progression-free survival (PFS). Patients with an A-LMR ≥ 1.0 experienced a superior OS and PFS versus patients with an A-LMR < 1.0 [median OS was not reached vs 17.9 months, 5-year OS rates of 87 % (95 % confidence interval (CI), 75–94 %) vs 26 % (95 % CI, 13–42 %), p < 0.0001; median PFS was not reached vs 11.9 months, 5-year PFS rates of 72 % (95 % CI, 58–83 %) vs 16 % (95 % CI, 6–32 %), p < 0.0001].ConclusionsA-LMR is also a prognostic factor for clinical outcomes in patients with T-cell lymphomas undergoing APHSCT.

Prognostic factors for clinical outcomes after rotator cuff repair.

OBJECTIVE: To identify prognostic factors of postoperative functional outcomes. METHODS: Retrospective case series evaluating patients undergoing rotator cuff repair, analyzed by the UCLA score (pre and 12-month postoperative) and Magnetic Resonance Imaging (preoperative). Patients' intrinsic variables related to the injury and intervention were evaluated. Multivariate linear regression analysis was performed to determine variables impact on postoperative functional assessment. RESULTS: 131 patients were included. The mean UCLA score increased from 13.17 ± 3.77 to 28.73 ± 6.09 (p<0,001). We obtained 65.7% of good and excellent results. Age (r= 0.232, p= 0.004) and reparability of posterosuperior injuries (r= 0.151, p= 0.043) correlated with the functional assessment at 12 months. After multivariate linear regression analysis, only age was associated (p = 0.008). CONCLUSIONS: The surgical treatment of rotator cuff tears lead to good and excellent results in 65.6% of patients. Age was an independent predictor factor with better clinical outcomes by UCLA score in older patients. Level of Evidence IV, Case Series.

Analysis of prognostic factors of clinical outcome in children and adolescents enrolled in phase I trials: a multicentre European collaborative study.

10049 Background: Phase I trials play a key role in the evaluation of novel agents for pediatric patients with advanced cancer. One of the major challenges remains the selection of patients who are...

Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

BackgroundAnemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.Methods249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003–2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.ResultsPatients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).ConclusionsWe found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define “high risk” populations in CKD.

The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia

Absolute lymphocyte count (ALC) after therapy has been reported to be an independent prognostic factor for clinical outcome in leukemia. This study mainly analyzed ALC at interim of therapy on day 22 (ALC-22) and the ratio of ALC-22 to ALC at diagnosis (ALC-0) on the impact of survival and the relation of ALC to lymphocyte subsets in 119 pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients. Univariate analysis revealed that ALC-22/ALC-0 ratio <10% was significantly associated with inferior overall survival (OS) (hazard ratio (HR)=12.24, P=0.0014) and event-free survival (EFS) (HR=3.3, P=0.0046). In multivariate analysis, ALC-22/ALC-0 ratio remained an independent prognostic factor for OS (HR=6.92, P=0.0181) and EFS (HR=2.78, P=0.0329) after adjusting for age, white blood cell (WBC) count and minimal residual disease (MRD) status. A Spearman correlation test showed that CD3+ T cells had a negative correlation with ALC-0 (r=−0.7204, P<0.0001) and a positive correlation with ALC-22 (r=0.5061, P=0.0071). These data suggest that ALC-22/ALC-0 ratio may serve as a more effective biomarker to predict survival in pediatric B-ALL and ALC is mainly associated with CD3+ T cells.

Relevance of αβ-DNTs as Prognostic Factor on Clinical Outcome and Role on Tumor Surveillance in Haematological Diseases and Solid Tumor: Preliminary Evaluations

The mutual interactions between the host immune system and cancer cells may either promote or control oncogenesis. Cancer immunotherapies remain viable approaches to sustain patient survival. However, positive clinical response of phase I/II clinical trials remains still to low. The Double negative T cells (DNTs) have emerged as new subset of T cells that contributes specifically to anti- tumor immunity since involved in immune regulation and tolerance acting as regulatory T cells (Treg) and/or cytotoxic T cells. DNTs express either αβ or γδ T-cell receptors (TCR) or lack CD4, CD8 and CD56. Functional studies showed that DNTs might have a direct in vitro anti-tumor activity against lymphoma and melanoma cells. However no data are available on their prognostic significance, modulation during the therapy response and their ability to kill tumor cells in cooperation with other immune cells such as DCs to explain their role in human anti-lymphoma immunity. Knowledge of the DNTs role in tumor surveillance and as prognostic factor for clinical outcome has a strong clinical valence and might allow us to design new approaches of therapeutic strategy.The aim of this study was to evaluate the DNTs during therapy response in lymph nodes (LN), bone marrow (BM) and peripheral blood (PB) of both lymphoma (Ly), Renal Cell Carcinoma (RCC) and Metastatic Melanoma (MM) patients (pts) in order to assess their role on clinical outcome, progression and tumor surveillance.PB and BM samples of 90 Ly pts, with NHL and cHL were collected at diagnosis and during the follow-up (1-6-12 months after chemo- or immuno-chemotherapy therapy). PB samples of 16 healthy donors were collected as control. Twenty fresh LN tissues from pts clinically suggestive of Ly were quickly processed. To evaluate the interaction of DNTs with tumor burden either 22 samples from RCC pts and 30 samples from MM pts were collected. The ontogeny, functional attitude and TCR clonality of DNT subsets (TCRαβ+ and TCRγδ+) were evaluated by following antibodies: CD3, CD4, CD8, CD56, CD45, TCRαβ, CD45Ra, CD45Ro, CCR7, CD27, CD28, CD30, CD69, GITR, CD95, CD178, CD152, IFN-γ, TNF-α, perforin and granzyme B. For functional studies, DNTs were purified from PBMCs through a negative selection and then cultured for 2 weeks. Data were acquired by 8-colour flow cytometer and analysed using Kaluza software. Other immune cells such as DCs, MDSCs and Treg was also detected to evaluate the correlation with DNTs. 7 cases of LNs received a finally diagnosis of reactive follicular hyperplasia (RFH) so they were considered as controls. All pts provided their informed consent in accordance with the Declaration of Helsinki.We observed a significant decrease (p =0.006) of circulating αβ-DNTs in untreated Ly pts (20.5 cells/ul ± 4.8) as compared with healthy controls (31.3 cells/ul ± 3.4) (fig.1-2) and their number seemed to be modulated during the follow-up. Their frequency in 1-month post-cht or disease relapsed pts was significantly decreased (p=0.006) as compared with the diagnosis as well as when compared indolent with aggressive histotypes (p=0.0001). In HL pts the frequency of αβ-DNT was significantly increased as compared with other histotypes (p=0.005) (Fig.3) Furthermore, the αβ-DNTs in LNs of Ly pts were significantly reduced as compared to to RFH-LNs (p=0.006) (fig.5) and are related to the aggressiveness of the disease. When evaluated either in MM and RRC pts the αβ-DNTs were significantly decreased (p=0.001) as compared with healthy controls and more interestingly when compared with Ly pts (p=0.001) given the greater immunological impairment of RCC/MM tumor burden (fig.6). Finally, ex vivo expanded DNTs acquired an immunomodulatory cytokine profile, characterized by the secretion of IFN-gamma and granzyme B, which are known as central components of anti-tumor immune responses supporting the hypothesis of αβ-DNT potential use in immunotherapeutic strategies (fig.4)Our preliminary data, showed an inverse correlation between the frequency of circulating αβ-DNTs and the tumor condition as well as that they could play an important role in both the development and the progression of lymphomas. This is the first study that compares the frequency of αβ-DNTs in three different pathologies correlating to tumor burden. In addition, it is likely that ex-vivo expanded DNTs exert an anti-tumor activity thus suggesting their possible use as a new strategy for adoptive immune-therapy. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Skull base atypical meningioma: Long term surgical outcome and prognostic factors

PurposeThe aim of this study was to examine the clinical outcomes of treating atypical meningioma at the skull base region following surgical resection and adjuvant radiotherapy, and to analyze the association between clinical characteristics and progression free survival. Materials and methodsTwenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed. ResultsThirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p=0.011). An older patient age at diagnosis also resulted in a worse outcome (p=0.024). An MIB-1 index <8% also contributed to improved PFS (p=0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p=0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up. ConclusionFor patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome.

Lymphopenia during routine follow-up may predict relapse in patients with extranodal NK/T cell lymphoma.

Recently, absolute lymphocyte count (ALC) at diagnosis, as a surrogate marker of host immunity, has been reported to be a prognostic factor for clinical outcomes in extranodal NK/T cell lymphoma (ENKTL). In this retrospective study, we set out to investigate whether ALC at the time of confirmed relapse or at last follow-up is a marker for relapse after chemoradiotherapy in 84 patients with stage I/II ENKTL. Receiver operating characteristics (ROC) curve and area under the curve (AUC) analysis showed that ALC at follow-up was a significant marker for relapse (AUC = 0.883, P < 0.001). Using 1.215 × 10(9)/L as the optimal cutoff value of ALC, 44 patients (52.4%) were in lower ALC group and 40 patients (47.6%) were in higher ALC group. The sensitivity and specificity for ALC at the time of confirmed relapse or at last follow-up was 94.1 and 76.0%, respectively. The relative risk of relapse with an ALC < 1.215 × 10(9)/L was 14.5. The positive predictive value with an ALC < 1.215 × 10(9)/L was 72.7%, and the negative predictive value with an ALC ≥ 1.215 × 10(9)/L was 95.0%. The 4-year cumulative incidence rate for an ALC < 1.215 × 10(9)/L was 73.2% compared with 3.2% for an ALC ≥ 1.215 × 10(9)/L (P < 0.001). In a multivariate regression analysis, ALC at the time of confirmed relapse or last follow-up remained to be a significant factor for relapse (P < 0.001). In conclusion, lymphopenia observed during routine follow-up can predict relapse in patients with ENKTL, which needs further validation in prospective trials.

Patients' perceived level of social isolation affects the prognosis of low back pain.

Perceived social isolation is prevalent among patients with low back pain (LBP) and could be a potential prognostic factor for clinical outcomes following an episode of LBP. A secondary analysis of an original prospective cohort study, which investigated the validity of the Danish version of the STarT Back Screening Tool (STarT), investigated whether social isolation predicts the clinical outcomes of disability, anxiety, depression and pain catastrophizing in people with LBP. Patients with LBP of any duration (N = 204) from Middelfart, Denmark, were included. Social isolation was measured at baseline using the friendship scale (score ranges from 0 to 24, with lower values meaning higher perceived social isolation), and outcomes were measured at baseline and at 6-month follow-up. Regression models investigated whether social isolation at baseline predicted the outcomes at 6-month follow-up. Some level of social isolation was reported by 39.2% of the participants (n = 80) with 5.9% (n = 12) being very socially isolated. One-point difference on social isolation predicted one point on a 100-point disability scale (adjusted unstandardized coefficient: -0.91; 95% confidence interval (CI): -1.56 to -0.26). Social isolation predicted anxiety; however, a change of one point on the social isolation scale represents a difference of only 0.08 points on a 22-point scale in anxiety (95% CI: 0.01-0.15) and is unlikely to denote clinical importance. Social isolation did not predict pain catastrophizing or depression. Patients' perceived social isolation predicts disability related to LBP. Further understanding of the role of social isolation in LBP is warranted.