Higher Relapse-free Survival Rate Research Articles

The clinicopathological significance and relapse predictive role of tumor microenvironment of intrahepatic cholangiocarcinoma after radical surgery.

This study attempts to detect the expression of FoxP3, CD68, CD8α, and PD-L1 in the tumor microenvironment (TME) of intrahepatic cholangiocarcinoma (ICC), and analyze the relationship between the corresponding cells and clinicopathological characteristics as well as prognosis of ICC. RNA sequencing (RNA-seq) provided the general landscape of the TME in ICC. A total of 99 ICC patients and the corresponding specimens were used for multiplex immunofluorescence and relapse-free survival (RFS) was analyzed. Flow cytometry further validated the effect of regulatory T (Treg) cells on ICC relapse. RNA-seq data showed that the infiltration of Treg cells, CD8+ T cells, and macrophages were likely associated with ICC relapse. The survival analysis based on multiplex immunofluorescence showed that the high FoxP3(+) Treg cells ratio and low CD68(+) macrophages ratio in mesenchyme were associated with higher RFS rate, respectively. Low FoxP3(+) Τreg cells ratio was associated with more perineural invasion, and high CD68(+) macrophages ratio was correlated with more lymph node metastasis. Cox regression analysis revealed that FoxP3(+) Treg cells ratio was an independent predictive factor for ICC relapse. Flow cytometry showed that TregIII was the predominant Treg cell subtype in both tumor tissue and peripheral blood of ICC patients, and high TregIII abundance in peripheral blood was significantly associated with longer RFS of ICC patients. High FoxP3(+) Treg cells ratio in the mesenchyme of ICC tumor tissue predicted longer RFS and was an independent favorable prognostic factor for ICC patients. Among all Treg cell subtypes, TregIII in peripheral blood was correlated with the RFS of ICC patients.

XPF -673C>T variation is associated with the susceptibility to breast cancer

PurposeXPF variations might decrease the DNA repair capacity and further contribute to cancer development. This study aimed to investigate the association of XPF polymorphisms with risk of developing breast cancer. MethodsTCGA, the Human Protein Atlas and Kaplan-Meier plotter were used to analyze the expression of XPF in breast cancer tissues and its effect on the survival of breast cancer patients. The expression of XPF in breast cancer tissues was detected by qRT-PCR. This case-control study included 467 breast cancer patients and 467 healthy controls. The genotype of genetic variation was detected by polymerase chain reaction restriction fragment length polymorphism. Odds ratios and 95 % confidence intervals were calculated. Correlations between XPF variation and clinicopathological parameters were assessed through Kendall’s Tau-b test. The relationship between XPF gene function variation and XPF gene expression was analyzed by GTEx. ResultsThe expression of XPF in breast cancer tissues is higher than that in normal tissues. Breast cancer patients with high XPF expression have a higher relapse free survival rate (HR = 0.88, 95 % CI = 0.80−0.97), but have no effect on the overall survival rate (logrank P = 0.28). XPF -673C > T variant can reduce the risk of breast cancer patients (OR = 0.35, 95 %CI = 0.20−0.63 for codominant mode; OR = 0.66, 95 %CI = 0.51−0.85 for dominant model; OR = 0.40, 95 %CI = 0.23−0.70 for recessive model). The XPF 11985 GG genotype reduced the risk of early breast cancer (OR = 0.49, 95 %CI = 0.24−0.97), but not the risk of advanced breast cancer (OR = 1.20, 95 % CI = 0.58−2.48). XPF 11985A > G variant can also reduce the risk of ERBB2 expression in patients (OR = 0.50, 95 %CI = 0.27−0.94). There is no correlation between XPF -673C > T/XPF11985A > G variants and ER and PR. XPF -673C > T variant can reduce XPF expression (P < 0.05). ConclusionsGenetic variations of XPF gene may affect its expression and the risk of breast cancer in the Chinese population.

Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study.

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

MP14-01 HYPOFRACTIONATED VERSUS CONVENTIONALLY FRACTIONATED RADIOTHERAPY FOR PROSTATE CANCER: 5-YEAR ONCOLOGIC OUTCOMES OF THE DUTCH RANDOMIZED PHASE 3 HYPRO TRIAL

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy1 Apr 2016MP14-01 HYPOFRACTIONATED VERSUS CONVENTIONALLY FRACTIONATED RADIOTHERAPY FOR PROSTATE CANCER: 5-YEAR ONCOLOGIC OUTCOMES OF THE DUTCH RANDOMIZED PHASE 3 HYPRO TRIAL Ruud Wortel, Luca Incrocci, Shafak Aluwini, Erik Schimmel, Stijn Krol, Peter-Paul van der Toorn, Hanja de Jager, Maarten Dirkx, Wendim Ghidey, Ben Heijmen, and Floris Pos Ruud WortelRuud Wortel More articles by this author , Luca IncrocciLuca Incrocci More articles by this author , Shafak AluwiniShafak Aluwini More articles by this author , Erik SchimmelErik Schimmel More articles by this author , Stijn KrolStijn Krol More articles by this author , Peter-Paul van der ToornPeter-Paul van der Toorn More articles by this author , Hanja de JagerHanja de Jager More articles by this author , Maarten DirkxMaarten Dirkx More articles by this author , Wendim GhideyWendim Ghidey More articles by this author , Ben HeijmenBen Heijmen More articles by this author , and Floris PosFloris Pos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2504AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hypofractionated radiotherapy might increase the radiobiological tumor dose without increasing toxicity due to the reported high radiation-fraction sensitivity of prostate cancer. Hypofractionated treatment is delivered in less fractions, offering both economic and logistical advantages. Here, we present the first results on oncologic outcome from the Dutch randomized HYPRO trial. METHODS Between 2007-2010, we conducted a multicenter, randomized phase 3 superiority trial, including intermediate-to high risk patients with localized T1b-4NX-0MX-0 prostate cancer. Inclusion criteria were a PSA concentration ≤60 ng/ml, and a WHO performance status 0-2. Patients were randomly assigned (1:1) to receive conventional treatment with 39 fractions of 2 Gy in 8 weeks, or hypofractionated treatment with 19 fractions of 3.4 Gy in 6.5 weeks. The primary endpoint is relapse-free survival (RFS) after treatment. Relapse is defined as biochemical relapse (Phoenix definition), clinical relapse, or start of hormonal therapy, whichever occurs first. The aim of this trial was to detect an absolute reduction of 10% of the relapse rate at 5 years in the hypofractionation arm. The Kaplan-Meier method was used to calculate RFS probabilities and Cox regression analysis was applied to compare the RFS between the treatment arms. Analyses were based on intention-to-treat. An α of 0.05 was considered the level of statistical significance. RESULTS Of the enrolled 820 patients, 804 men were included in this analysis. Median follow-up was 60 months. Androgen deprivation therapy (ADT) was prescribed to 534 patients (66%). The 5-year RFS rates were 77% for conventional treatment and 80% for hypofractionated treatment (p=0.36)(Figure 1). The adjusted hazard ratio (HR) was 0.86 (95% CI 0.63-1.16). Factors associated with RFS in multivariate analysis were Gleason score ≤7 (HR=0.46, 95% CI 0.3-0.7, p<0.001), long-term ADT (≥12 months) vs none (HR=0.50, 95% CI 0.3-0.8, p=0.004), and >25% risk of seminal vesicle involvement (HR=2.59, 95% CI 1.4-4.9, p=0.004). CONCLUSIONS Hypofractionated radiotherapy (19 fractions of 3.4 Gy) resulted in higher RFS rates, but we found no evidence of superiority of hypofractionation over conventional treatment. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e142-e143 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ruud Wortel More articles by this author Luca Incrocci More articles by this author Shafak Aluwini More articles by this author Erik Schimmel More articles by this author Stijn Krol More articles by this author Peter-Paul van der Toorn More articles by this author Hanja de Jager More articles by this author Maarten Dirkx More articles by this author Wendim Ghidey More articles by this author Ben Heijmen More articles by this author Floris Pos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications. Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C). According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n=6); Before-S or N and After-C, Group II (n=9); and Before-S or N and After-S or N, Group III (n=8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups. CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

Long-term prognostic impact of circulating tumour cells in gastric cancer patients.

AIMTo analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery.METHODSA 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated.RESULTSThe median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034).CONCLUSIONA lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

The influence of infection early after allogeneic stem cell transplantation on the risk of leukemic relapse and graft‐versus‐host disease

An infection after allogeneic stem cell transplantation (SCT) can affect the activity of immune cells and increase the level of proinflammatory cytokines. Further, a post-SCT infection may influence the milieu of the graft-versus-leukemia (GVL) effect and graft-versus-host disease (GVHD). We performed a retrospective study of patients with acute leukemia who had undergone allogeneic SCT using the same preparative regimens and bone marrow as the stem cell source to determine if early post-transplant infection was associated with the risk of leukemic relapse and GVHD. The analysis revealed that patients who had a febrile infection (FI) before post-transplant day 21 (FI group) had a lower actuarial probability of leukemic relapse (P < 0.001) and a higher relapse-free survival rate (P = 0.012) than those patients who did not have a FI before post-transplant day 21 (non-FI group). The experience of early post-transplant FI (HR = 0.316; 95% CI = 0.174-0.575; P < 0.001), together with the presence of chronic GVHD and high risk cytogenetics, were independent predictive factors for post-transplant leukemic relapse. The FI group had a trend towards a higher lymphocyte count on post-transplant day 21 than the non-FI group (P = 0.063), despite the delayed recovery of the platelet count and a trend towards delayed recovery of the neutrophil count. These findings suggest that a change in the immunologic network by infectious diseases in the early post-transplant period favors the milieu of the GVL effect. The specific immunologic change during FI, which can potentiate the GVL effect, remains to be determined.

Retrospective assessment of quality of life and treatment outcome in patients with Hodgkin's disease from 1969 to 1994

We determined the current quality of life (QoL) of patients with Hodgkin's disease treated at the Innsbruck University Hospital between 1969 and 1994 at a mean time of 9.1±7.0 years after their initial treatment. Further aims of our study were to assess potential differences in objective treatment outcome and QoL between patients treated with chemo-, radio- or combined modality therapy and those enrolled in randomised clinical trials or treated according to standard procedures. The QLQ-C30, a health-related and validated self-report questionnaire developed by the Study Group on Quality of Life of the European Organization for Research and Treatment of Cancer (EORTC) was mailed to a cohort of 194 survivors out of a total of 225 patients with Hodgkin's disease; 126 of them (64.9%) returned the completed questionnaire. The 5- and 10-year overall survival rates for the total group of 225 patients were 94.3% and 84.9%, respectively. Irrespective of stage, higher relapse-free survival rates were observed in patients receiving combined modality treatment ( P=0.025). Five-year relapse-free survival rates were 96.6% for patients enrolled in clinical trials and 82.8% for patients treated outside of randomised studies ( P=0.037 in univariate and P=0.064 in multivariate analysis). Patients treated with combined modality regimens had reduced QoL scores in comparison with those treated with either radiation or chemotherapy alone, but QoL parameters did not differ between patients enrolled in clinical trials and those treated according to standard procedures. Patients with Hodgkin's disease had an excellent long-term prognosis and very high QoL scores a mean of 9.1 years after treatment of their disease. The improved relapse-free survival rates achieved by combined modality regimens must be carefully weighed against the accompanying reduced QoL, since lower relapse rates did not translate into a survival advantage.