Duration Of Disease-free Survival Research Articles

CD56 and CD11b Positivity with Low Smac/DIABLO Expression as Predictors of Chemoresistance in Acute Myeloid Leukaemia: Flow Cytometric Analysis

Background:Resistance to chemotherapy is a major obstacle to curing acute myeloid leukaemia (AML), and several antigens are claimed to play primary roles in this resistance.Purpose:The aim of this study was to evaluate the roles of CD56, CD11b and Smac/DIABLO gene expression levels as prognostic markers of the clinical outcome, response to chemotherapy and survival of AML patients.Materials and Methods:A cross-sectional observational study was conducted on 60 naïve-AML patients who received induction therapy with mitoxantrone and cytarabine combined with a high dose of cytarabine. The CD56,CD11b and Smac/DIABLO expression levels were assessed using flow cytometry at diagnosis and were analysed for correlation with the possible associated risk factors, response to chemotherapy, and median duration of disease-free survival (DFS) and overall survival (OS).Results:The overall results revealed that AML patients who exhibited positive expression for CD56 and CD11b had short median durations of DFS and OS.(P = 0.019, 0.006, 0.029 and 0.024, respectively). Additionally, low Smac/DIABLO expression had a negative impact on treatment outcome in terms of CR rate (p=0.012) and reduced DFS (p=0.000) and OS(p=0.000) values.Conclusions:CD56 and CD11b positivity and low Smac/DIABLO expression are important predictive factors for the occurrence of chemoresistance, in addition to other risk factors, among AML patients.

Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation

AbstractWe investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation (aSCT). Ninety-seven Ph+ ALL patients (median age 41 years; range 18-64 years) within the prospective multicenter German Multicenter ALL Study Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with single nucleotide polymorphism arrays and validated by multiplex ligation-dependent probe amplification. The frequencies of recurrently deleted genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6, 5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival (P = .023), disease-free survival (P = .012), and remission duration (P = .036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase 1 and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT.

Peritumoral overexpression of ZBP-89 is associated with unfavorable disease-free survival rates in patients with hepatocellular carcinoma following hepatectomy.

Previous studies have revealed that the peritumoral environment has a profound influence on tumor initiation and progression. Zinc-binding protein-89 (ZBP-89) has been observed to be involved with tumor development, recurrence, and metastasis. High intratumoral expression of ZBP-89 has been associated with improved prognosis in several tumor types. However, the prognostic values of peritumoral expression of ZBP-89 remain to be elucidated in patients with hepatocellular carcinoma (HCC) following curative resection. In the present study, peritumoral ZBP-89 expression was examined using immunohistochemistry in 102 HCC patients who had received curative hepatectomy. Expression of ZBP-89 protein was positive in 66.3% of the peritumoral samples from 102 HCC patients. HCC patients with high peritumoral ZBP-89 expression exhibited significantly shorter disease-free survival (DFS) times (P=0.012) than those patients with low peritumoral ZBP-89 expression. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis. Univariate and multivariate Cox proportional hazard regression analyses demonstrated that albumin levels ≤35 g/l, multiple tumors, tumor sizes ≥5 cm, and macroscopic vascular invasion may serve as independent prognostic factors for overall survival (OS) [hazard ratio (HR)=2.031; P=0.014] in patients with HCC. The multivariate Cox regression model identified that high ZBP-89 expression, multiple tumors and macroscopic vascular invasion were independent prognostic factors for shorter DFS durations. High expression of ZBP-89 in peritumoral HCC tissues was associated with a shorter DFS in HCC patients following curative hepatectomy. Additionally, high ZBP-89 expression in peritumoral HCC tissue was positively associated with the presence of liver cirrhosis in HCC patients, indicating that cirrhosis accompanied by high ZBP-89 expression may be a contributing factor to the poor prognosis of patients with HCC. Therefore, peritumoral ZBP-89 expression may be a good prognostic marker to predict DFS time in HCC patients following curative hepatectomy and may provide novel insights into the molecular mechanisms of HCC initiation.

Clinicopathologic and survival results in serous endometrium carcinoma and subgroup analysis for mixed serous and pure serous histology.

Objective:To review the clinicopathologic and survival outcomes of patients with serous endometrial cancer (EC) and to investigate subgroup analysis based on pure serous and mixed serous EC subtypes.Material and Methods:Patients who underwent EC surgery between 2002 and 2014 and who were reported as serous EC were enrolled in the study. All patients were diagnosed as having serous EC or mixed serous EC with serous component higher than 10% based on the postoperative pathology report.Results:A total of 93 patients were analyzed. The median disease-free and overall survival (OS) durations were 49.6 and 32.2 months, respectively. Forty-three patients (46.2%) relapsed and 35 patients (37.6%) died. The histologic type was pure serous EC in 52 (55.9%) and mixed EC in 41 (44.9%) patients. There was no statistical difference between the pure serous and mixed serous groups in terms of age, International Federation of Gynecology and Obstetrics stage, lymphadenectomy, lymph node metastasis or adjuvant therapy combinations. Twenty-nine (55.8%) patients in the pure serous group and 14 (34.1%) in the mixed serous group hade recurrence (p=0.038). Twenty-five (48.1%) patients in the pure serous group and 10 (24.4%) in the mixed serous group died (p=0.034). In the pure serous group, the mean disease-free and OS durations were shorter than in the mixed serous group (59 vs. 81 months and 73 vs. 95 months, log-rank p=0.055 and 0.041, respectively). Histologic type was a significant prognostic factor on recurrence and OS in the univariate analysis (Hazard ratio: 2.404, 95% Confidence interval: 1.01-5.71; 2.027, respectively), but not in the multivariate analysis, which included disease stage and age of the patients.Conclusion:Compared with pure serous and mixed serous endometrium cancer groups, primary surgical treatments, clinicopathologic features and adjuvant treatments were similar, but there was a survival difference. Patients with pure serous cancer had a worse prognosis. However histology was not an independent factor for survival.

Re: Adjuvant Sunitinib in High-risk Renal-cell Carcinoma After Nephrectomy

BackgroundSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. MethodsIn this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. ResultsThe median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo gr...

Lung metastasectomy in renal cell carcinoma: Evaluation of 20 cases

Aim: About 90% of kidney cancers are renal cell carcinoma (RCC), and one-third of them are metastatic at the time of diagnosis. Most RCC metastases are to the lung. In this article, we present the results of a series of pulmonary metastasectomies for RCC in our institute. Materials and Methods: Twenty cases who underwent pulmonary metastasectomy for RCC between 2007 and 2017 were retrospectively reviewed. Patients were classified according to the age, sex, smoking history, duration of disease-free survival, number of metastatic lesions, median survival time, survival time after metastasectomy, type of surgery, and whether they received immunotherapy. Results: Fifteen of the patients were male and five were female. The mean age was 60-year-old (range: 28–86-year-old). Nineteen of the 20 patients had a history of nephrectomy. The median disease-free survival time was found to be 16.5 months while the median survival time after nephrectomy was 43.3 months. The number of detected metastatic lesions ranged from one to eight, and the location of the majority of them was intraparenchymal. Survival time after metastasectomy was found to be 20.6 months. Surgical approaches included bilateral metastasectomy through median sternotomy, unilateral wedge resection, and lobectomy through video-assisted thoracoscopic surgery or thoracotomy. Conclusion: The results of a combination of pulmonary metastasectomy and immunotherapy treatment were found to be better than immunotherapy or surgery alone. However, further study is needed with a larger series to support this argument.

Vismodegib for Locally Advanced Periocular and Orbital Basal Cell Carcinoma: A Review of 15 Consecutive Cases.

Summary:Basal cell carcinoma (BCC) is the most common periocular skin cancer and can lead to significant morbidity. We assess the effectiveness of vismodegib, a first-in-class Hedgehog signaling pathway inhibitor, in the management of periocular and orbital BCCs based on clinical response, tolerability, and orbital content preservation. All patients with periocular or orbital BCCs who met criteria for vismodegib treatment were recruited prospectively between May 2012 and 2014 from 2 hospitals. Patients received oral vismodegib (150 mg daily) until disease progression, unacceptable toxicity, or withdrawal. All patients were followed up monthly. Patient demographics, tumor size, treatment duration including dosing regimen, adverse events, response rate, duration of response, progression-free survival, and disease-free survival were analyzed. All 15 patients had biopsy-proven BCCs with no metastatic disease at presentation. The mean age was 74 years and 10 patients (67%) had orbital involvement. The mean lesion longest dimension was 51 mm and 7 cases (47%) represented recurrence following previous surgery and/or radiotherapy. The mean treatment duration was 13 months and mean follow-up duration 36 months. Ten patients (67%) had a complete response, 3 (20%) had a partial response, and 2 had progressive disease following an initial partial response (13%). The partial response of 55% in 1 patient allowed subsequent surgical resection with clear margins. Vismodegib is effective for treating periocular and orbital BCCs with orbital salvage of patients who otherwise would have required exenteration. There is a neoadjuvant role for vismodegib but further studies are required.

Curative Resection of Single Primary Hepatic Malignancy: Liver Imaging Reporting and Data System Category LR-M Portends a Worse Prognosis

The purpose of this study was to examine the associations between preoperative Liver Imaging Reporting and Data System (LI-RADS) categories and prognosis after curative resection of single hepatic malignancies in patients with chronic liver disease. Between January 2008 and December 2010, 225 patients with chronic liver disease underwent resection of single hepatic malignant tumors (218 hepatocellular carcinomas, three cholangiocarcinomas, four biphenotypic carcinomas) after undergoing gadoxetic acid-enhanced MRI. Two radiologists retrospectively categorized the tumors into LI-RADS categories. Differences in disease-free survival duration between categories were analyzed by the Kaplan-Meier method with the log-rank test. Reviewer 1 categorized two (0.9%) patients as having LR-3, 53 (23.6%) LR-4, 159 (70.7%) LR-5, and 11 (4.9%) LR-M lesions. The corresponding numbers for reviewer 2 were six (2.7%) LR-3, 30 (13.3%) LR-4, 178 (79.1%) LR-5, and 11 (4.9%) LR-M. The 2-year cumulative recurrence or death rates were 15.1% for lesions categorized LR-3 or LR-4 by reviewer 1, 31.7% for LR-5, and 60% for LR-M. For lesions categorized by reviewer 2 the corresponding rates were 20.6% for LR-3 or LR-4, 29% for LR-5, and 54.5% for LR-M. Disease-free survival was significantly worse among patients with lesions categorized as LR-M than for lesions categorized as LR-3 or LR-4 or as LR-5 (p < 0.01 for both reviewers). Disease-free survival did not significantly differ between patients with LR-3 or LR-4 and those with LR-5 lesions (reviewer 1, p = 0.301; reviewer 2, p = 0.291). Patients with tumors preoperatively categorized as LR-M may have a worse prognosis than those with tumors categorized LR-3, LR-4, or LR-5 after curative resection of single hepatic malignancy.

Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases.

Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor β, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.

Invasive Pleomorphic Lobular Histology is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer

Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage and more aggressive clinical course. Patients with IPLC reveal poorer prognostic factors such as higher histological grade, relative lower percentages of hormone positivity, and increased rate of recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it is observed that current treatment methods for IPLC do not seem as successful as in ILC and failed to be effective. Thence, individual therapies including more aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier stages of breast cancer should be performed for this distinct variant.

Prediction of Recurrence by Preoperative Intratumoral FDG Uptake Heterogeneity in Endometrioid Endometrial Cancer

PURPOSE: To investigate the prognostic value of preoperative intratumoral 18F-FDG uptake heterogeneity (IFH) derived from positron emission tomography (PET)/computed tomography (CT) in patients with endometrioid endometrial cancer. METHODS: We retrospectively evaluated clinicopathological data from patients with pathologically proven endometrioid endometrial cancer who had undergone 18F-FDG PET/CT scans before surgery. Patients were divided into two groups according to their IFH. The main outcome measure was disease-free survival (DFS). RESULTS: Between January 2010 and January 2015, data from 72 patients were available for analysis. The median duration of DFS was 23 months (range, 6 to 57 months), and 4 (5.6%) patients experienced recurrence. There were significant differences in tumor size, IFH, and DFS between patients with and without recurrence. In regression analysis, high IFH value [P = .007, hazard ratio (HR) 2.545, 95% confidence interval (CI) 1.468-8.674] was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P < .001, log-rank test). CONCLUSIONS: Preoperative IFH measured by 18F-FDG PET/CT was associated with recurrence of endometrioid endometrial cancer. The finding supports evidence that FDG-based heterogeneity can be a novel and useful predictor of endometrioid endometrial cancer recurrence.

Clinical characteristics and prognosis of non-B, non-C hepatocellular carcinoma: The impact of patient sex on disease-free survival - A retrospective cohort study

BackgroundThe number of patients with hepatocellular carcinoma (HCC) negative for both hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) has increased recently. The purpose of the present study was to investigate the clinical characteristics and prognoses of non-B non-C HCC (NBNC-HCC) patients. Materials and methodsFrom January 2000 to December 2013, 154 patients with NBNC-HCC and 560 patients with HBsAg or HCVAb positive (BC)-HCC who underwent curative resection were analyzed retrospectively. The clinical features of NBNC-HCC and BC-HCC were compared, and the prognoses of NBNC-HCC patients were analyzed. ResultsIn comparison to patients with BC-HCC, patients with NBNC-HCC had better liver function but higher pathological tumor stages. The disease-free survival (DFS) duration was significantly higher in patients with NBNC-HCC than it was in those with BC-HCC. In patients with NBNC-HCC, aspartate aminotransferase ≥40 IU/L, albumin level <3.5 g/dL, and multiple tumors were independent risk factors of overall survival; and male sex and multiple tumors were independent risk factors of DFS. ConclusionPatients with NBNC-HCC had significantly longer DFS durations than those with BC-HCC. The patient sex had an impact on the postsurgical outcomes of patients with NBNC-HCC in DFS.

Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis.

AIMTo investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict the prognosis of hepatocellular carcinoma (HCC) patients with portal/hepatic vein tumor thrombosis (PVTT/HVTT) after hepatectomy.METHODSThe study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed.RESULTSOverall survival (OS) and disease-free survival (DFS) were determined in the patients with a high (> 2.9) and low (≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group (OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS (P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni- and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score (r = 0.276, P = 0.015) and the maximum diameter of the tumor (r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients.CONCLUSIONThe preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma.

AIMTo clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging.RESULTSThe median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy

BackgroundSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.MethodsIn this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.ResultsThe median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.ConclusionsAmong patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674.)

The Prognosis of Adult Burkitt’s Cell Leukemia in Real-Life Clinical Practice

Objective:Many studies reported an improved prognosis in patients with Burkitt’s lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt’s cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions.Materials and Methods:In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups.Results:The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients.Conclusion:DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer

For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18months). The median age and tumor size was 72years and 2.5cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7months. The DFS rate was 58.3% and 53.2% at 1 and 3years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0months; P=.02) and OS (31.4 vs 14.3months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and "elsewhere lung" (20.8%). The median time to each was 5 to 7months. From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50Gy) with chemotherapy should be considered a standard option.

Prognostic significance of tumor deposits in patients with stage Ⅲ colon cancer

Objective: To investigate the prognostic significance of tumor deposits (TD) in patients with stage Ⅲ colorectal cancer who underwent radical resection. Methods: We retrospectively analyzed the clinicopathological data, and the impact of tumor deposits on the disease free survival (DFS) and overall survival (OS) in 206 patients with stage Ⅲ colorectal cancer using Kaplan-Meier and Cox regression analyses. Results: Among the 206 patients with stage Ⅲ colorectal cancer, there were 112 (54.4%) tumor deposit-positive (TD+ ) cases and 94 (45.6%) tumor deposit-negative (TD-) cases. The TD- and TD+ cases accounted for 10.6% and 21.4% of patients aged <50 years, 22.3% and 36.6% of patients with poorly differentiated carcinoma, and 16% and 29.5% of patients with neural invasion, respectively (P<0.05 for all). In addition, the neural invasion was more often found along with the increasing number of TD. However, multivariate analysis showed that TD was not significantly associated with DFS and OS of the patients. Among the patients with N1 stage cancer, the 3-year DFS rates of TD+ and TD- groups were 23.0% and 58.8%, and the median disease-free survival durations were 26 months and 43 months, respectively (P=0.002). Meanwhile, in the TD- group, the 3-year DFS rates in the patients with stage N1a~1b without tumor deposit and N1c cancer were 63.5% and 21.2%, and the median disease-free survival durations were 41 and 25 months, respectively (P=0.004). Conclusions: Tumor deposit is an independent unfavorable prognostic factor affecting the DFS. The number of tumor deposits may be an important factor affecting prognosis in stage Ⅲ colorectal cancer patients. Tumor deposits after radical resection are associated with neural invasion, and can be used as an independent factor of poor prognostic evaluation in patients with stage N1 colorectal cancer.

RING1 and YY1 binding protein suppresses breast cancer growth and metastasis.

Evidence suggests that RING1 and YY1 binding protein (RYBP) functions as a tumor suppressor. However, its role in breast cancer remains unclear. In the present study, the expression of RYBP was assessed in breast cancer patients and cell lines. Disease-free survival durations of breast cancer patients with high RYBP expression were determined based on the ATCG dataset. The effects of RYBP overexpression on cell growth, migration and invasive potency were also assessed. Nude mouse xenograft and lung metastasis models were also used to confirm the role of RYBP. The involvement of SRRM3 in RYBP-mediated breast cancer suppression was explored using SRRM3 siRNA. The potential relationship between RYBP, SRRM3, and REST-003 was examined by qPCR. The results showed that RYBP was downregulated in breast cancer patients and in several breast cancer cell lines. Breast cancer patients with high expression levels of RYBP displayed better disease-free survival. Overexpression of RYBP in MDA-MB-231 and SK-BR-3 cells significantly decreased cell proliferation, migration, and invasion ability, and increased the proportion of cells arrested in S-phase compared with the negative control cells. Additionally, upregulation of proliferation-related cell cycle proteins (cyclinA and cyclinB1) and E-cadherin, and downregulation of snail were observed in RYBP-overexpressing cells. Overexpression of RYBP reduced tumor volume and weight as well as metastatic foci in the lungs of nude mice. SRRM3 knockdown by siRNA, which is downregulated after RYBP overexpression, suppressed cell growth and metastasis in MDA-MB-231 and SK-BR-3 cells. Furthermore, qPCR analysis revealed that REST-003 ncRNA was downregulated in cells overexpressing RYBP and in SRRM3-inhibited cells. Moreover, cell invasion ability and growth were increased after SRRM3 upregulation in RYBP-overexpressing cells, but they were decreased following si-REST-003 transfection. In conclusion, overexpression of RYBP suppresses breast cancer growth and metastasis both invitro and invivo. SRRM3 and REST-003, which are downregulated in cells overexpressing RYBP, may be involved in RYBP-mediated breast cancer progression.

Clinical characteristics of triple negative breast cancer in Egyptian women: a hospital-based experience

Purpose: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis despite the high rates of response to chemotherapy. We aim to study the clinical features, factors influencing recurrence and survival outcomes of TNBC patients. Methods: We retrospectively studied the charts of patients with biopsy proven TNBC treated at The Clinical Oncology Department Ain-Shams University between 2009 and 2012. Results: One hundred and forty five patients fulfilled the eligibility criteria. The incidence of TNBC was 10.5% - 15% with a mean of 12% of all breast cancer patients. The follow-up duration ranged from six months to four years. The age range was 26 to 78 years. Infiltrating ductal carcinoma represented 93.1% of the pathologic types. 87% of patients were free of metastases (M0) at presentation. Clinical stages II and III represented 38 and 39.5% of the patients. 66% of patients had modified radical mastectomy. Following surgery, 77.5% of patients received adjuvant chemotherapy while 61% of the patients had adjuvant radiation therapy. Anthracyclines based chemotherapy was given to 52% of patients. Disease-free survival (DFS) of the M0 patients at 20 and 30 months was 92% and 80% respectively. Relapse occurred in 23% of M0 patients. After a mean duration of DFS of 15.1 months, the most common sites of metastases for relapsed M0 patients were pulmonary (44.8%), bone (41.4%), and locoregional (13.8%). The median overall survival (ORS) of patients was 18 months (1 - 45 months), whereas for the M1 group of patients the median ORS was 9 months (2 - 29 months). Conclusion: The incidence, pathological characteristics, and clinical behavior of TNBC were similar to what is mentioned in the literature. Adding taxanes to the chemotherapy protocols and using postoperative radiotherapy were both associated with a significant increase in the mean period of DFS, while did not significantly affect the ORS.