eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

Bone Metabolism Discrepancy in Type 2 Diabetes Mellitus Patients With and Without Non-Alcoholic Fatty Liver Disease

To explore the distribution of several bone metabolic indicators in type 2 diabetes patients (T2DM) with and without non-alcoholic fatty liver disease (NAFLD) and to preliminarily evaluate the relationship of bone metabolism with NAFLD in patients with T2DM. The hospitalized patients with T2DM were divided into the group of T2DM complicated with NAFLD and the group of T2DM alone according to the results of ultrasonic diagnosis. The general information and laboratory test data such as bone metabolism indexes of these patients were collected and the differences of the indexes between the 2 groups were compared. Furthermore, the independent influencing factors of NAFLD in patients with T2DM were analyzed. A total of 186 patients were included in the study. Compared with patients with T2DM only, patients with T2DM combined with NAFLD were characterized with younger age (p < 0.001), higher BMI (p = 0.016), ALT (p = 0.001), TG (p = 0.005), HOMA-IR (p = 0.005), and lower HDL-C (p = 0.031). Significant discrepancy of age (OR 1.052, p = 0.001), ALT (OR 0.964, p = 0.047), HOMA-IR (OR 0.801, p = 0.005), and T-PINP (OR 1.022, p = 0.008) was found using multivariate logistic regression model. Significant discrepancy of T-PINP was found in T2DM patients with and without NAFLD. Further studies are needed to explore whether T-PINP could be used as a predictor of fatty liver disease, osteoporosis, and other related complications in patients with T2DM.     

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients

BackgroundExtra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions.MethodsAll patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012–December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates.ResultsFrom 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up.ConclusionsThe majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

Referral patterns and outcomes of a highly specialised pelvic exenteration multidisciplinary team meeting: A retrospective cohort study

IntroductionThe purpose of this study was to review recommendations made from a specialist pelvic exenteration (PE) multidisciplinary team (MDT) and to provide insights as to the impact of the MDT on patient selection and clinical decision making.Materials & methodsA retrospective review was conducted at Royal Prince Alfred Hospital's PE MDT between June 2014 and December 2015. Data was collected from the recorded minutes of MDT meetings. Referral information and clinical data was extracted from individual patient files. Additional data including operative dates and surgical resection margins were collected from electronic medical records.ResultsOf the 183 patients considered for PE during the MDT meeting, 104 (57%) were recommended for surgery. Factors that influenced the recommendation in favour of surgery were referral by a surgeon (P = 0.004), referral from a rural location (P = 0.05) and having locally advanced primary cancer (P < 0.001). Patients who were seen by the unit's surgeon prior to the MDT did not impact on the MDT recommendation nor the decision for or against surgery (P = 0.771). The most common reason for recommendation against PE was unresectable distant metastatic disease (43%).ConclusionsThe PE MDT meeting is a critical step in the patient care pathway and facilitates critical decision making. Anatomically-based contraindications to surgery (i.e. involvement of adjacent organs, bone and neurovascular structures) do not appear to influence MDT decision making regarding resectability.     

Overall survival and PD-L1 expression in patients with recurrent or metastatic head and neck cancer treated with nivolumab

ObjectiveOur facility measures programmed cell death ligand 1 (PD-L1) expression in all patients before administering nivolumab. The aim of the present study is to clarify the association between overall survival (OS) and PD-L1 expression.Patients and MethodsSubjects in this study were 52 patients with R/M-HNC cancer (45 men, 7 women) administered nivolumab in our facility between June 1, 2017 and January 31, 2019. Mean age was 62.2 years (median, 65 years; range, 28–81 years). Histopathological type was squamous cell carcinoma (SCC) in 48 cases, and non-SCC in 4 cases. We set OS as the primary endpoint and progression-free survival (PFS), overall response rate (ORR), association of OS and PD-L1 expression and association of PFS and PD-L1 expression as secondary endpoints. The cut-off for PD-L1 expression was set using the receiver operating characteristic (ROC) curve. We compared OS, PES and ORR using this PD-L1 cut-off for all patients and for the SCC group. OS and PFS were calculated using Kaplan-Meier methods. The log-rank test was used for statistical analysis, with values of p < 0.05 taken as significant. For PD-L1 immunohistochemistry assays, Dako 28-8 antibody was used.ResultsIn the all-patients group, median OS was 9.6 months and 1-year OS rate was 40.4%. Median PFS was 4.0 months and 1-year PFS rate was 37.8%. The cut-off value of PD-L1 expression for OS was 40% for all patients and the SCC group. When PD-L1 expression was ≥40%, OS was significantly better in both all patients and the SCC group (p = 0.004, 0.007). The cut-off value of PD-L1 expression for PFS was also 40%. When PD-L1 expression was ≥40%, PFS was better in all patients and the SCC group (P = 0.003, 0.009). In the all-patients group, ORR was 19.2% and disease control rate (DCR) was 44.2%. When PD-L1 expression was ≥40%, ORR was 44.4% and DCR 83.3%.ConclusionIn the present study, when PD-L1 expression was high (≥40%), OS was significantly better (p = 0.004). This finding has not been reported in other research on R/M-HNC. PFS and ORR were also better with high PD-L1 expression. Regarding patterns of progression with a PD-L1 expression cut-off of 40%, hyperprogression was significantly more frequent for PD-L1 expression <40% (p = 0.039). Therefore, high PD-L1 expression could offer a predictor of prognosis and efficacy for nivolumab. The present findings may prove useful in considering treatment strategies.