Cumulative Disease-free Survival Research Articles

The expression of Eps15 homology domain 1 is negatively correlated with disease-free survival and overall survival of osteosarcoma patients

BackgroundOsteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the occurrence of osteosarcoma was important for its prediction and prevention. To investigate the usefulness of mammalian Eps15 homology domain 1 (EHD1) as a prognostic marker for osteosarcoma, the expression of EHD1 in 57 osteosarcoma patients was measured using immunohistochemistry techniques and correlated with the clinicopathological features of patients.MethodsCorrelations of EHD1 expression levels with clinicopathological features of patients were assessed using the Pearson χ2 test for categorical variables and the Student t test for continuous variables. Cumulative disease-free survival (DFS) curves and overall survival (OS) curves were plotted using the Kaplan–Meier method, and the relationship between each of the variables and survival was assessed by log-rank tests using univariate analysis. Subsequently, the parameters were tested using the multivariate Cox proportional hazards model, which was used to identify independent variables for predicting survival. EHD1 expression [P = 0.020; HR, 5.582; 95% confidence intervals (CI), 1.314–23.72] was an independent prognostic indicator of DFS in osteosarcoma patients; tumor size and EHD1 expression of osteosarcomas were independent prognostic indicators of OS in osteosarcoma patients.ResultsEHD1 protein expression was a positive expression in examined tumor tissues. The median OS time of patients with high expression of EHD1 was 46.8 months (95% CI, 29.8–63.8 months), and the median OS time of patients with low expression of EHD1 was 58.8 months (95% CI, 31.6–86.0 months). The prognosis for patients with low expression of EHD1 in osteosarcomas was significantly better than that for patients with high expression of EHD1 (log-rank test, P = 0.019).ConclusionThe expression of EHD1 was negatively correlated with DFS and OS of osteosarcoma patients; therefore, the expression of EHD1 is a prognostic marker for prediction and prevention of osteosarcomas.

C14orf166 Is a Biomarker for Predicting Hepatocellular Carcinoma Recurrence

Aim: Chromosome 14 open reading frame 166 (C14orf166) acts as a transcriptional repressor and is correlated with centrosome architecture manipulation. Nevertheless, the function of C14orf166 in hepatocellular carcinoma (HCC) progression remains unclear. We aimed to investigate the role C14orf166 plays in HCC and further compared the prognostic value of C14orf166 with that of clinicopathological features. Methods: C14orf166 expression was evaluated in a human liver cell line, HCC cell lines, HCC tissues and adjacent noncancerous liver tissues with qRT-PCR, western blot and immunohistochemistry. Patients were divided into two different groups according to C14orf166 level. The relationship between C14orf166 expression and clinicopathological features was assessed by Pearson chi-squared test and receiver operating characteristic curves. Cumulative disease-free survival (DFS) and overall survival (OS) curves were evaluated using the Kaplan–Meier method. Results: C14orf166 mRNA and protein expression is upregulated in HCC cell lines and tissues. The level of C14orf166 was correlated with serum alpha-fetoprotein level, lymph node metastasis, tumor size and recurrence, with high C14orf166 expression correlating with high HCC recurrence risk. The poor OS and DFS of HCC patients are partly due to the persistently high HCC recurrence risk. When combined with serum alpha-fetoprotein level, the predictive accuracy of C14orf166 for HCC recurrence was enhanced (AUC = 0.712, 95% CI 0.603–0.821; p = 0.001). Conclusions: This study demonstrated that C14orf166 is a high-risk biomarker and predictive factor for HCC recurrence, providing information for the selection of appropriate treatment strategies.

Hepatic resection vs percutaneous radiofrequency ablation of hepatocellular carcinoma abutting right diaphragm.

BACKGROUNDIt is usually difficult to adequately conduct percutaneous ultrasound-guided radiofrequency (RF) ablation for hepatocellular carcinomas (HCCs) abutting the diaphragm. Our hypothesis was that the subphrenic location of HCC could have an effect on the long-term therapeutic outcomes after hepatic resection and RF ablation.AIMTo compare the long-term therapeutic outcomes of hepatic resection and percutaneous RF ablation for HCCs abutting the diaphragm.METHODSA total of 143 Child-Pugh class A patients who had undergone hepatic resection (n = 80) or percutaneous ultrasound-guided RF ablation (n = 63) for an HCC (≤ 3 cm) abutting the right diaphragm were included. Cumulative local tumor progression (LTP), cumulative intrahepatic distant recurrence (IDR), disease-free survival (DFS), and overall survival (OS) rates were estimated. Prognostic factors for DFS and OS were analyzed. Complications were evaluated.RESULTSThe cumulative IDR rate, DFS rate, and OS rate for the hepatic resection group and RF ablation group at 5 years were “35.9% vs 65.8%”, “64.1% vs 18.3%”, and “88.4% vs 68.7%”, respectively. Hepatic resection was an independent prognostic factor for DFS (P ≤ 0.001; hazard ratio, 0.352; 95%CI: 0.205, 0.605; with RF ablation as the reference category); however, treatment modality was not an independent prognostic factor for OS. The LTP rate was 46.6% at 5 years for the RF ablation group. The major complication rate was not significantly different between the groups (P = 0.630). The rate of occurrence of peritoneal seeding was higher in the RF ablation group (1.3% vs 9.5%, P = 0.044).CONCLUSIONAlthough OS was not significantly different between patients who had gone hepatic resection or percutaneous RF ablation for HCCs abutting the diaphragm, DFS was better in the hepatic resection group.

Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma: Does the Degree of Ethiodized Oil Accumulation within the Tumor Affect the Therapeutic Efficacy?

PurposeTo evaluate the effects of the degree of ethiodized oil accumulation achieved by transarterial chemoembolization followed by radiofrequency (RF) ablation on the treatment efficacy for a single intermediate-sized hepatocellular carcinoma (HCC). Materials and MethodsA total of 153 consecutive patients who underwent chemoembolization and RF ablation for a single intermediate-sized HCC (2–5 cm) were included. On the basis of the degree of ethiodized oil accumulation in HCC on cone-beam CT images, patients who underwent chemoembolization and RF ablation were classified into 2 groups: compact accumulation (≥ 75%) and noncompact accumulation (< 75%). The rates of cumulative local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between groups. ResultsOf the 153 patients, 89 were classified into the compact ethiodized oil accumulation group and 64 in the noncompact ethiodized oil accumulation group. There were no significant differences in patient demographic or HCC characteristics between groups except for the incidence of liver cirrhosis (P = .038) and the tumor margin morphology (P = .008). The cumulative LTP rate was significantly lower in the compact accumulation group than in the noncompact accumulation group (P = .013). There were no significant differences in the incidences of complications, DFS rates (P = .055), or OS rates (P = .184). ConclusionsThe degree of ethiodized oil accumulation does not play a role in decreasing the OS or DFS rate after chemoembolization and RF ablation for intermediate-sized HCC; however, it may contribute to reducing the rate of LTP.

Is there a patient population with squamous cell carcinoma of the head and neck region who might benefit from de-intensification of postoperative radiotherapy?

The aim of this retrospective study was to evaluate the clinical outcome of apreviously defined low-risk patient population with completely resected (R0) squamous cell carcinoma of the oral cavity, oropharynx, larynx (pT1-3, pN0-pN2b), hypopharynx (pT1-2, pN0-pN1), and the indication for postoperative radio(chemo)therapy. According to predefined criteria, 99patients with head and neck squamous cell carcinoma (SCC) who were treated at our institution from January1, 2005 to December31, 2014, were available for analysis. The Kaplan-Meier method was used for calculating survival and incidence rates. For univariate comparative analysis, the log-rank test was used for analyzing prognostic clinicopathologic parameters. Median follow-up was 67months. Cumulative overall (OS) and disease-free survival (DFS) were 97.9%/94.7%/88.0% and 96.9%/92.6%/84.7% after 1, 2, and 5years, respectively. Cumulative incidence of loco-regional recurrence (LRR), distant metastases (DM), and second cancer (SC) were 1.0%/1.0%/4.9%, 0.0%/3.4%/5.8%, and 2.1%/4.2%/13.1%, respectively. In univariate comparative analysis, location of the primary tumor in the oropharynx was asignificant predictor for increased OS (p = 0.043) and DFS (p = 0.048). Considering the low disease relapse rates and high rates of therapy-induced late side effects, as well as the increased risk of developing SC, aprospective multicentric trial investigating de-escalation of radiotherapy in this clearly defined low-risk patient population was started and is still recruiting patients (DIREKHT-Trial, NCT02528955).

Long-term Survival Outcomes of Laparoscopic Gastrectomy for Advanced Gastric Cancer: Five-year Results of a Phase II Prospective Clinical Trial.

PurposeDespite an increased acceptance of laparoscopic gastrectomy (LG) in early gastric cancer (EGC), there is insufficient evidence for its oncological safety in advanced gastric cancer (AGC). This is a prospective phase II clinical trial to evaluate the feasibility of LG with D2 lymph node dissection (LND) in AGC.Materials and MethodsThe primary endpoint was set as 3-year disease-free survival (DFS). The eligibility criteria were as follows: 20-80 years of age, cT2N0-cT4aN3, American Society of Anesthesiologists score of 3 or less, and no other malignancy. Patients were enrolled in this single-arm study between November 2008 and May 2012. Exclusion criteria included cT4b or M1, or having final pathologic results as EGC. All patients underwent D2 lymphadenectomy. Three-year DFS rates were estimated by the Kaplan-Meier method.ResultsA total of 157 patients were enrolled. The overall local complication rate was 10.2%. Conversion to open surgery occurred in 11 patients (7.0%). The mean follow-up period was 55.0±20.4 months (1–81 months). The cumulative 3-year DFS rates were 76.3% for all stages, and 100%, 89.3%, 100%, 88.0%, 71.4%, and 35.3% for stage IB, IIA, IIB, IIIA, IIIB, and IIIC, respectively. Recurrence was observed in 37 patients (23.6%), including hematogenous (n=6), peritoneal (n=13), locoregional (n=1), distant node (n=8), and mixed recurrence (n=9).ConclusionsIn addition to being technically feasible for treatment of AGC in terms of morbidity, LG with D2 LND for locally advanced gastric cancer showed acceptable 3-year DFS outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT01441336

The Impact of Adjuvant Radiation Therapy and Elective Nodal Irradiation in Early Stage/Low Grade versus Advanced Stage/High Grade Olfactory Neuroblastoma

Olfactory neuroblastoma (ONB) is a rare head and neck cancer originating from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. Several retrospective studies have shown surgical resection, followed by adjuvant radiotherapy, to be superior to either modality alone. However, even with bi-modality or even tri-modality therapy ONB patients with high Hyams grade (HHG) and advanced Kadish stages (AKS), C or D, have worse clinical outcomes compared to low Hyams grade (LHG) and early Kadish stages (EKS), A or B. This study evaluates clinical outcomes in ONB patients, comparing adjuvant radiation therapy versus surgery alone in EKS. In addition we evaluated the impact of adjuvant radiotherapy including elective nodal irradiation (ENI). Forty-one ONB patients treated with surgical resection at our institution from 1996 to 2017 were identified. Two patients died following surgery and were excluded from the analysis. Univariate, multivariate, and survival analysis was performed with comparative analysis between radiation of the primary site and ENI. Median follow-up time in this cohort was 59 months (range 5.2-236). The median overall survival (OS) and disease free survival (DFS) for the entire cohort was 15 years and 7.6 years, respectively. The five-year cumulative OS and DFS was 83% and 72%, respectively. Ten patients (26%) had ONBs classified as EKS and 29 patients (75%) had AKS tumors. The 5 year OS for ONBs with LHG was 100% compared to 65% for those with ONBs with HHG (p=.017). 66% of the EKS patients were also LHG compared to only 28% LHG in AKS patients (p=.057). The 5 year OS/DFS was 100%/100%, 100%/66%, 100%/75%, and 59%/47% for EKS/LHG, EKS/HHG, AKS/LHG, and AKS/HHG, respectively (p=0.07). Five patients in the EKS group received surgical resection alone, and there were no observed deaths or recurrences with a median follow up of 44 months (range 5-235 months). 31 (79%) patients in the entire cohort presented with node-negative disease. 13 (56%) of the node-negative patients received ENI. There were six nodal-failures in the entire cohort, with one failure 16 years following treatment (median 59 months, range 6-165 months). In node-negative patients the 10 year nodal-failure rate was reduced from 38% (3/8) in patients treated with primary site radiation alone to 0% (0/9) with the addition of ENI (p=.04). In this retrospective review, patients with both AKS and HHG have significant worse clinical outcomes compared to EKS and LHG. In EKS patients, surgery alone resulted in long term OS and DFS. For patients with node negative disease at presentation (other than those with EKS who did not undergo radiation), ENI resulted in significant reduction in the regional failure. In select patients presenting EKS and LHG ONB, surgical resection alone can be considered. Furthermore ENI should be standard of radiation therapy and long term follow up is recommended.

Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma

目的研究外周血造血干细胞移植治疗外周T细胞淋巴瘤（PTCL）的疗效。方法回顾性分析解放军总医院血液科2007年6月至2017年6月接受外周血造血干细胞移植PTCL患者的临床资料。结果共有41例PTCL患者纳入研究，男30例，女11例，中位年龄38（13~57）岁。17例行自体外周血造血干细胞移植（auto-PBSCT），24例行异基因外周血造血干细胞移植（allo-PBSCT）。auto-PBSCT组ALK阳性间变大细胞淋巴瘤占47.1%（8/17），allo-PBSCT组NK/T细胞淋巴瘤和外周T细胞淋巴瘤-非特指型占66.7%（16/24）。auto-PBSCT组患者移植前疾病处于完全缓解（CR）状态者占58.8%（10/17），疾病进展（PD）状态者占11.8%（2/17）；allo-PBSCT组移植前疾病状态为CR者8.3%（2/24），PD者45.8%（11/24）。auto-PBSCT组和allo-PBSCT组移植后2年总生存率、无病生存率差异均无统计学意义[（64.0±10.8）%对（53.5±9.7）%，P=0.543；（57.1±12.4）%对（53.5±10.6）%，P=0.701]。auto-PBSCT组6例死亡，5例死于复发；allo-PBSCT组12例死亡，其中5例死于复发，7例为移植相关死亡。结论auto-PBSCT和allo-PBSCT均是PTCL的有效治疗方法。

Expression and clinical significance of short-chain dehydrogenase/reductase 16C5 in human pancreatic cancer tissues and cell lines

Objective By studying the expression level of short-chain dehydrogenase/reductase 16C5 (SDR16C5) in human pancreatic cancer to determine whether SDR16C5 is associated with the prognosis of pancreatoduodenectomy. Methods Immunohistochemistery staining was used to detect the expression level of SDR16C5 in 100 human pancreatic cancer tissues and 30 paracancer tissues. Western blotting and real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) was used to detect the protein and mRNA expression level of SDR16C5 in pancreatic cancer cell lines and immortalized pancreatic ductal epithelial cell line. Kaplan-Meier method and multivariate COX regression analysis was used to analyze the effect of SDR16C5 expression on the prognosis of pancreatoduodenectomy. Results The expression level of SDR16C5 was not associated with gender, age, tumor diameter, tumor location and portal vein invasion in pancreatic cancer patients. The expression level of SDR16C5 in pancreatic cancer tissues and pancreatic cancer cell lines was significantly higher than in adjacent tissues and immortalized pancreatic ductal epithelial cell lines (P=0.001). The expression level of SDR16C5 in patients with poorly differentiated pancreatic cancer was significantly higher than that in medium and well differentiated pancreatic cancer (χ2=42.46, P=0.001). SDR16C5 expression was significantly higher in patients with local lymph node metastasis than in patients without local lymph node metastasis (χ2=8.94, P=0.003). The expression of SDR16C5 in TNM stage Ⅲ patients was significantly higher than that in TNMⅠ and Ⅱ patients (χ2=8.94, P=0.003). The recurrence rate of those medium and high expression of SDR16C5 was significantly higher than in low expression patients (χ2=39.02, P=0.001). The cumulative disease-free (χ2=6.29, P=0.012) and overall (χ2=11.63, P=0.001) survival rate of these patients with high expression of SDR16C5 was significantly lower than that of low expression. Multivariate COX regression analysis showed that SDR16C5 was an independent risk factor for the prognosis of pancreaticoduodenectomy. Conclusion SDR16C5 is up-regulated in pancreatic cancer tissues and pancreatic cancer cell lines. Detection of SDR16C5 helps to determine the prognosis. Key words: Short-chain dehydrogenase/reductase 16C 5; Pancreatic cancer; Prognosis

Autophagy related markers (Beclin-1 and ATG4B) are strongly expressed in Wilms' tumor and correlate with favorable histology.

Wilms' tumor treatment has achieved great success in the last decade. Nevertheless, some cases still fail to respond to the current multimodality therapy. These cases fall mainly in the unfavorable histology group with very few belonging to the favorable histology group. In recent years, autophagy manipulation whether inhibition or stimulation has been shown to affect cancer cell behavior and has emerged as a novel mechanism to improve cancer cell response to currently used therapeutic regimens. The current study aimed to investigate the expression of autophagy related markers (ATG4B and Beclin1) in WT, its association with the different clinic-pathological parameters and its impact on patient survival. Twenty-one formalin fixed paraffin embedded (FFPE) WT specimens were immunohistochemically stained using autophagy related markers; Beclin-1 and ATG4B. All clinical, radiological and follow up data were retrieved from the patient records. All specimens showed positive expression of both Beclin-1 and ATG4B. The staining score for Beclin1 varied between 50 and 300, and its expression was significantly associated with favorable histology (p=0.007). Similarly, ATG4B expression was significantly higher in favorable histology tumors compared to unfavorable histology (p=0.046). A statistically significant positive correlation between Beclin-1 and ATG4B expression was observed. The cumulative disease-free survival in patients with favorable histology was significantly higher compared to patients with unfavorable histology (p=0.0027). Beclin-1 and ATG4B expression were both found to be statistically significant discriminators of survival. Collectively these findings suggest that the expression of autophagy-related markers is associated with a favorable histology and could predict better survival in these patients.

Associations between Tensin1 protein and clinicopathological characteristics and prognoses of gastric cancer patients

Objective To investigate the associations between expression of Tensin1 protein and clinicpathological characteristics and prognoses of gastric cancer (GC) patients. Methods The retrospective case-control study was conducted. The clinicopathological data of 163 GC patients who were admitted to the Affiliated Hospital of Jiangsu University between July 31, 2011 and December 31, 2013 were collected. The GC tissues and adjacent normal tissues were taken to paraffin imbedding, and then were detected by immunohistochemistry. Observation indicator: (1) expressions of Tensin1 protein in GC tissues and adjacent normal tissues; (2) association between expression of Tensin1 protein in GC tissues and clinicopathological characteristics; (3) follow-up and survival situations; (4) prognostic factors analysis. Follow-up using telephone interview was performed to detect survival up to January 1, 2017. Measurement data with skewed distribution were described as M (range). Count data were analyzed using the chi-square test or pairing chi-square test. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method, and Log-rank test was used for survival analysis. The univariate analysis and multivariate analysis were done using the COX roportional hazard model. Results (1) Expressions of Tensin1 protein in GC tissues and adjacent normal tissues: immunohistochemistry showed that Tensin1 protein in GC tissues and adjacent normal tissues mainly expressed in cytoplasm. Of 163 patients, 154 (66 with high expression and 88 with low expression) and 9 had respectively positive and negative expressions of Tensin1 protein in GC tissues; 79 (37 with high expression and 42 with low expression) and 84 had respectively positive and negative expressions of Tensin1 protein in adjacent normal tissues, with statistically significant differences in positive expression ratio and expression levels (χ2=64.65, 12.93, P<0.05). (2) Association between expression of Tensin1 protein in GC tissues and clinicopathological characteristics: high expression rate of Tensin1 protein in GC tissues were respectively 31.34%(21/67) in GC patients with tumor metastases and 46.88%(45/96) in GC patients without tumor metastasis, with a statistically significant difference (χ2=3.95, P<0.05). (3) Follow-up and survival situations: all the 163 patients were followed up for 3.3-64.7 months, with a median time of 28.7 months. The 3-year cumulative disease-free survival rate and cumulative overall survival rate in GC tissues were 63.12%, 74.22% in 66 patients with high expression of Tensin1 protein and 47.30%, 55.74% in 97 patients with low and negative expressions of Tensin1 protein, showing statistically significant differences in above indicators (χ2=4.58, 4.11, P<0.05). Survival analysis of subgroups showed that 3-year cumulative disease-free survival rate in GC tissues of patients with maximum tumor dimension ≥ 5 cm, nerve and / or vascular invasions and stage Ⅲ of TNM staging were 45.98%, 62.79%, 52.75% in patients with high expression of Tensin1 protein and 18.11%, 31.10%, 32.80% in patients with low and negative expressions of Tensin1 protein, with a statistically significant difference (χ2=5.85, 7.89, 4.96, P<0.05). The 3-year cumulative overall survival rate was respectively 66.00%, 75.75%, 67.93% in patients with high expression of Tensin1 protein and 30.74%, 40.15%, 44.67% in patients with low and negative expressions of Tensin1 protein, with statistically significant differences (χ2=7.59, 9.62, 4.32, P<0.05). (4) Prognostic factors analysis: results of univariate analysis showed that maximum tumor dimension, histological grade, nerve and / or vascular invasions, postoperative TNM staging, postoperative adjuvant chemotherapy and expression of Tensin1 protein were related factors affecting prognoses of GC patients [hazard ratio (HR)=3.66, 2.45, 2.17, 3.36, 0.41, 0.54, 95% confidence interval (CI): 2.09-6.41, 1.43-4.19, 1.17-4.04, 1.52-7.41, 0.23-0.72, 0.31-0.96, P<0.05]. Results of multivariate analysis showed that maximum tumor dimension ≥ 5 cm and grade Ⅲ of histological grade were independent risk factors affecting prognoses of GC patients (HR=3.21, 2.17, 95%CI: 1.63-6.32, 1.18-3.99, P<0.05), and postoperative adjuvant chemotherapy and high expression of Tensin1 protein were independent protective factors affecting prognoses of GC patients (HR=0.50, 0.44, 95%CI: 0.28-0.90, 0.24-0.82, P<0.05). Conclusion High expression of Tensin1 protein may inhibit GC metastasis, and it is also an independent protective factor affecting prognoses of GC patients. Key words: Gastric neoplasms; Tensin1; Clinicopathological characteristics; Prognosis; Survival rate

Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial

The impact of the intensity of conditioning before allogeneic haemopoietic cell transplantation (HCT) has been studied in a randomised phase 3 trial comparing reduced-intensity conditioning with myeloablative conditioning in patients with acute myeloid leukaemia in first complete remission. Because of the short follow-up of the original trial, whether reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning remained unclear. To address this question, we present retrospective 10-year follow-up data of this trial and focus on late relapse. The original randomised phase 3 trial included patients aged 18-60 years, with intermediate-risk or high-risk acute myeloid leukaemia, an adequate organ function, and an available HLA-matched sibling donor or an unrelated donor with at least nine out of ten HLA alleles matched. Patients were randomly assigned (1:1) to 120 mg/m2 fludarabine combined with four 2 Gy doses of total-body irradiation (reduced-intensity conditioning) or six 2 Gy doses of total-body irradiation and 120 mg/kg cyclophosphamide (myeloablative conditioning). The primary and secondary efficacy endpoints of this trial have been published previously. In this retrospective, long-term follow-up analysis, data were collected from medical reports from individual participating study centres, and from physician and patient interviews. Endpoints included in this analysis were cumulative relapse incidence, overall survival, disease-free survival, and non-relapse mortality in the original study population and in patients alive and relapse-free at 12 months after HCT (landmark analysis). 10-year time to event rates were calculated in the intention-to-treat population and were compared with the Gray test. The trial is registered with ClinicalTrials.gov, number NCT00150878. In the original trial, 195 patients were randomly assigned to receive reduced-intensity conditioning (n=99) or myeloablative conditioning (n=96). For this retrospective analysis, data were collected with a nearly complete follow-up (completeness index 99%). Median follow-up time for surviving patients was 9·9 years (IQR 8·5-11·4), during which the cumulative incidence of relapse in the complete study population was identical in both groups (30% [95% CI 20-39] in the reduced-intensity conditioning group vs 30% [21-40] in the myeloablative conditioning group; Gray test p=0·99). Relapse occurred at a median of 5·0 months (IQR 3·0-8·8) in the reduced-intensity conditioning group versus 9·5 months (4·5-20·5) in the myeloablative conditioning group. 10-year disease-free survival was 55% (95% CI 45-66) in the reduced-intensity conditioning group and 43% (34-55) in the myeloablative conditioning group (hazard ratio [HR] 0·76 [0·51-1·14]; p=0·19). 10-year non-relapse mortality was 16% (95% CI 8-24) in the reduced-intensity conditioning group and 26% (17-36) in the myeloablative conditioning group (subdistribution HR 0·60 [95% CI 0·32-1·11]; Gray test p=0·10). The incidence of long-term toxicities associated with total-body irradiation was comparable; secondary malignancies occurred in six (6%) of 94 patients in the reduced-intensity conditioning group and five (6%) of 90 in the myeloablative conditioning group (p=1·00). There is no evidence that reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning. Given that the reduced-intensity conditioning group in the original trial was associated with lower early morbidity and toxicity, reduced-intensity conditioning with moderately reduced total-body irradiation doses could be the preferred conditioning strategy for patients with acute myeloid leukaemia who are younger than 60 years and transplanted in first complete remission. None.

Osteosarcoma of the jaw: Challenges in the diagnosis and treatment

PurposeOsteosarcomas rarely affect jaw bones. Patients are usually older than those who suffer long bone sarcomas, with a rare incidence of metastasis. This is suggestive of a different pattern of behavior compared with long bone sarcomas. This study aimed to present NCI, Cairo University experience in treating patients diagnosed with osteosarcomas of the jaw, including the diagnostic challenges and treatment outcome. Patients and methodsThis is a retrospective case series study of all cases of osteosarcomas of mandible and maxilla that were treated at the NCI, in the period between 2006 and 2013. Patients' data, including demographic data, various clinical presentations, results of investigations, treatment modalities performed and outcomes, were collected from hospital records kept in the Biostatistics Department at NCI. ResultsRecords showed 21 cases of osteosarcoma of the jaw. The mandible was affected in 15 cases, the maxilla in six. Two cases had sun-ray periosteal reactions. Erroneous biopsy results were found in 4 cases compared with final pathology reports of surgical resections. All cases underwent surgical resections, with 8 cases having positive margins. The median follow-up period was 19.3 months (range 0.3–98.0 months). The cumulative disease-free survival (DFS) was 27.5% and the median DFS was 72 months. The cumulative overall survival at end of the study was 77.4%. ConclusionsOsteosarcoma of the jaw is challenging both to diagnose and manage. This is due to the high incidence of mistakes in biopsy results, rare specific radiological features and difficulties in proper resection due to proximity to vital structures.

Preservation of the nipple-areola complex in skin-sparing mastectomy for early breast cancer.

Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer while overcoming the cosmetic issues related to surgery. We review our experience of performing SSMs and assess whether preservation of the nipple-areola complex (NAC) could have been an option for some patients who underwent SSM. The subjects of this retrospective study were women who underwent SSM that utilized four incision types; namely, the so-called tennis racket incision, a periareolar and midaxillary incision, an areola-sparing and midaxillary incision, and a small transverse elliptical incision. We assessed whether preservation of the NAC would have been an option in SSM, based on histologic examination of three serial cut surfaces of the specimen around the nipple, ruling out the option when evidence of the malignant lesion/s was found in at least one of the following locations: in the nipple, within a 1-cm radius from the base of the nipple, or within 1cm from the surface of the NAC. We performed 193 SSMs. The cumulative 10-year local disease-free survival rate was 98%, with 89% of patients reporting levels of satisfaction with the reconstructed breast, of excellent, very good, or good. We evaluated that 70 of the 193 procedures could have been performed as nipple-sparing mastectomy (NSM). The outcomes of SSM in this series were excellent and NSM might have been an option for about one-third of the patients.

Addition of oxaliplatin to capecitabine-based preoperative chemoradiotherapy for locally advanced rectal cancer: Long-term outcome of a phase II study.

Our previous study reported the favorable short-term outcome and good tolerance of integrating oxaliplatin into capecitabine-based (XELOX regimen) preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). The present study reported the long-term oncological outcome of this phase II study. A total of 47 patients with rectal adenocarcinoma (stage II or III) were enrolled and received radiotherapy (46 Gy in 23 fractions) in combination with capecitabine (1,000 mg/m2, twice daily, on days 1–14 and 22–35) and oxaliplatin (130 mg/m2 on days 1 and 22). Overall survival (OS) rate, disease-free survival (DFS) rate and cumulative incidence of recurrences and long-term complications were calculated or observed. As a result, 41 patients underwent surgery after preoperative CRT, and the cumulative OS rates at 1, 3 and 5 years for these patients were 100.0, 84.5 and 81.8%, respectively. For the 38 patients who received R0 resection, the cumulative OS rates at 1, 3 and 5 years were 100.0, 89.0 and 86.2%, respectively, while the cumulative DFS rates at 1, 3 and 5 years were 94.6, 75.3 and 69.7%, respectively. After follow-up at 84 months, the cumulative incidence rates of local and distant recurrences at 5 years were 6.6 and 28.2%, respectively. Oxaliplatin-associated long-term complications were seldom observed. Overall, the addition of oxaliplatin to capecitabine-based preoperative radiotherapy achieved favorable OS and DFS without increased long-term complications in patients with LARC. Therefore, this preoperative CRT strategy is a feasible option for such patients.

Efficacy and Safety of Co-transplantation of Haploidentical-HSC with Umbilical Cord Mesenchymal Stem Cell in Children with Hematologic Malignancies

To analyse the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cell(UC-MSC) with haploidentical hematopoietic stem cell transplantation(hi-HSCT) in children with hematologic malignancy. The clinical data of 47 children undergoing hi-HSCT were retrospectively analyzed from November 2003 to November 2014, among them 34 patients received UC-MSC from October 2011 to November 2014, and another 13 patients without UC-MSC from November 2003 to September 2011. The median follow-up time was 20(0.5-67) months. No adverse events were observed after the UC-MSC transplantation. The engraftment rate, the median neutrophils engraftment time and platelet engraftment time all were not significantly different between hi-HSCT and hi-HSCT+UC-MSCT(P>0.05). The three-years cumulative overall survival (70.6% vs 23.1%),(P=0.004), three-years cumulative disease-free survival(52.9% vs 0) (P=0), and early cytomegalovirus (CMV) viremia (91.2% vs 38.5%) (P=0) in UC-MSC+hi-HSCT group were statistically significantly higher than that in the conventional hi-HSCT group. The morbidity of aGVHD (44.1% vs 92.3%) (P=0.003), I-II aGVHD (26.5% vs 61.5%) (P=0.041) and transplantation-related mortality (11.8% vs 46.2%) (P=0.017) in UC-MSC+hi-HSCT group was statistically significantly lower than that in hi-HSCT group, however, the morbidity of III-IV aGVHD (17.6% vs 30.8%), cGVHD (26.5% vs 30.8%), HC (35.3% vs 7.7%), pulmonary infection (52.9% vs 46.2%) and relapse rate (32.4% vs 53.8%) were not statistically significantly different (P>0.05) between the 2 groups. The application of umbilical cord mesenchymal stem cell in children undergoing hi-HSCT is safe, the UC-MSC can improve the overall survival, disease-free survival and reduce transplantation-related mortality. UC-MSC can reduce the morbidity of aGVHD, but increase the early infection of CMV, however it is nothing for the pulmonary infection and relapse in the children after hi-HSCT.

Percutaneous microwave ablation of renal cancers under CT guidance: safety and efficacy with a 2-year follow-up

To evaluate the safety and efficiency of percutaneous microwave ablation (MWA) of renal cell carcinomas (RCC) carried out under computed tomography (CT) guidance. A retrospective study was performed on RCC that was either histologically proven or diagnosed at imaging (Bosniak IV cyst) and treated by MWA under general anaesthesia with CT guidance. Indications for percutaneous ablation were based on the American Urological Association recommendations. Twenty-four months post-procedure follow-up was performed. Sixty-two patients presenting one or more RCC (84 tumours ranging from 10-48mm in diameter; mean diameter: 25.6mm) were included. Technical success was achieved for 78 tumours (58 patients). For four patients, the treatment was stopped due to gas dissection failure. At 3months, six residual tumours were observed (8%). At 6months, two recurrences and one residual tumour (3.8%) were observed; all were retreated with complete success. At 12months, local control of the disease was achieved in 94% of cases (100% in cases where treatment was performed). Two cases of distal metastasis were observed after 12 and 24months. At 24months, one patient presented with a contralateral tumour. The complication rate was 4.8% including one grade III complication and two grade II complications according to the Clavien-Dindo classification. At 2years, the cumulative disease-free survival rate and overall survival were 95% and 97%, respectively. MWA ablation under CT guidance to treat RCC is safe and provides a high rate of effectiveness at 24months.

Association of T-cell infiltration assessed in pretherapeutic biopsies (PTB) of patients with locally advanced rectal adenocarcinoma (LARC) with tumor response and relapse after chemoradiotherapy (CRT) and rectal surgery.

3599 Background: Pre-operative CRT followed by total mesorectal excision (TME) is nowadays the standard of care for patient with LARC (cT3-T4N0 or cTxN+). Currently, pathologic complete response occurs in +/- 15% after CRT. Colorectal cancer T-cell infiltration is a strong prognostic factor for survival after primary tumor resection. Our aim was to determine whether T-cell infiltration in PTB could be predictive of tumor response and relapse after CRT + TME. Methods: Between 1999 and 2012, patients with LARC who underwent CRT + TME and with available clinical follow-up and PTB (with sufficient tumor cells density) were identified at the Cliniques universitaires St-Luc. The density of CD3 (T cells) and CD8 (cytotoxic) was quantified on immunostained PTB slides and analyzed with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Cumulative disease-free survival (DFS) was performed using the Kaplan-Meier estimator and compared by log-rank tests. Cox regression we used for uni- and multi-variate analysis. P value of less than 0.05 was considered statistically significant. Results: 154 patients (sex ratio M/F 1.8; mean age 65 years-old; upper (20%), mid (29%) and low rectum (51%), synchronous metastases (11%)) were analyzed. High CD3 and CD8 PTB densities were significantly associated with a higher pathological response (Dworak 3-4) and lower ypTNM stage after CRT +TME (p &lt; 0,05). Higher CD3 and CD8 PTB densities were associated with higher patient DFS (CD3: HR = 2,30 (CI95%:1,15-4,59) p = 0,02; CD8: HR = 1,95 (CI95%: 1,01-3,75) p = 0,04). These results were confirmed in uni and multivariate analysis. CD3 and CD8 PTB densities added to pathological response (ypTNM/Dworak) but also clinical response (ycTNM) after CRT + TME increases significantly the accuracy prediction of tumor relapse. Conclusions: Pretherapeutic T-cell infiltration of LARC is predictive of tumor response and relapse after CRT +TME. This biomarker could be helpful for patient treatment decision. It must be validated in larger patient cohorts.

MiR-15a-5p, A Novel Prognostic Biomarker, Predicting Recurrent Colorectal Adenocarcinoma.

Colorectal cancer is one of the most common gastrointestinal diseases and the second leading cause of cancer-associated deaths among adults. miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a transcription factor essential for prolonged cancer cell proliferation and survival. In the current study, we assessed the potential diagnostic and prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma. To accomplish this goal, total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-15a-5p expression was analyzed using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry. SNORD43 (RNU43) was used as an internal control gene. miR-15a-5p was significantly upregulated in colorectal tumors compared to non-cancerous colorectal mucosae, while ROC analysis suggested its potential use for diagnostic purposes. Moreover, miR-15a-5p overexpression predicts poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox regression analysis confirmed that miR-15a-5p overexpression is a significant unfavorable prognosticator of DFS in colorectal adenocarcinoma, independent of other established prognostic factors plus treatment of patients. Importantly, miR-15a-5p overexpression retains its unfavorable prognostic value in patients with T3 colorectal adenocarcinoma and in those without distant metastasis (M0). More importantly, the cumulative DFS probability of patients with early stage disease was significantly lower for those with colorectal adenocarcinoma overexpressing miR-15a-5p. In conclusion, elevated expression of the cancer-associated miR-15a-5p predicts poor DFS and OS of colorectal adenocarcinoma patients. The prognostic value of miR-15a-5p expression regarding DFS is independent of clinicopathological factors currently used for colorectal adenocarcinoma prognosis.

Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A

The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child–Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P < 0.0001); DFS at 5 years postoperatively in these two groups was 45.9 and 34.0%, respectively (P < 0.0013). Both double- and triple-positive tumor markers are associated with early recurrence and poor survival in HCC patients within the Milan criteria and Child–Pugh class A.