Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the ...therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.
Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.
Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0–78.2) with nivolumab plus SOX and 76.5% (50.1–93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8–NR) and 10.6 months (5.6–12.5), respectively.
Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.
NCT02746796.
There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have ...failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10mg/kg by intravenous infusion every 2weeks or physician’s choice of chemotherapy (paclitaxel 80mg/m2 on days 1, 8, and 15 or irinotecan 150mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0months; hazard ratio (HR)=1.1 95% confidence interval (CI) 0.9–1.4; P=0.81} or the secondary end points of PFS median, 1.4 versus 2.7months; HR=1.73 (95% CI 1.4–2.2); P>0.99 or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
ClinicalTrials.gov: NCT02625623.
Background
The aim of this study was to compare the results of laparoscopy‐assisted total gastrectomy with those of open total gastrectomy for early gastric cancer.
Methods
Patients with gastric ...cancer who underwent total gastrectomy with curative intent in three Korean tertiary hospitals between January 2003 and December 2010 were included in this multicentre, retrospective, propensity score‐matched cohort study. Cox proportional hazards regression models were used to evaluate the association between operation method and survival.
Results
A total of 753 patients with early gastric cancer were included in the study. There were no significant differences in the matched cohort for overall survival (hazard ratio (HR) for laparoscopy‐assisted versus open total gastrectomy 0·96, 95 per cent c.i. 0·57 to 1·65) or recurrence‐free survival (HR 2·20, 0·51 to 9·52). The patterns of recurrence were no different between the two groups. The severity of complications, according to the Clavien–Dindo classification, was similar in both groups. The most common complications were anastomosis‐related in the laparoscopy‐assisted group (8·0 per cent versus 4·2 per cent in the open group; P = 0·015) and wound‐related in the open group (1·6 versus 5·6 per cent respectively; P = 0·003). Postoperative death was more common in the laparoscopy‐assisted group (1·6 versus 0·2 per cent; P = 0·045).
Conclusion
Laparoscopy‐assisted total gastrectomy for early gastric cancer is feasible in terms of long‐term results, including survival and recurrence. However, a higher postoperative mortality rate and an increased risk of anastomotic leakage after laparoscopic‐assisted total gastrectomy are of concern.
Feasible but high risk of anastomotic complication
To assess the histological response and the reinforcing effects of bone ingrowth within porous hydroxyapatite (HA) implants depending on pore geometry, four kinds of cylindrical-type with parallel ...linear pores (
φ50, 100, 300, 500
μm), one kind of sponge-type with irregular interconnecting pores (
φ250
μm) and one cross-type with crossing linear pores (
φ100×120
μm) of porous HA were prepared. Eighty-four rabbits were divided into six groups, and a 5×5×7
mm sized porous HA block was inserted through the medial cortical window of the proximal tibia. Histomorphological changes were examined using light and scanning electron microscopy. A biomechanical compression test was performed using material test machines. After implantation, the implants showed different histological changes depending on pore geometry. Active osteoconduction was also found in the
φ50
μm sized cylindrical-type porous HA. Evidence of remodeling of new bone and bone marrow formation within porous HA was found in the larger cylindrical-types (
φ300, 500
μm), and the sponge- and cross-types. The biomechanical test showed that the ultimate compressive strength increased significantly in the
φ300
μm sized cylindrical-type, and in the sponge- and cross-types eight weeks after implantation. Porous HA with cylindrical pores could be a useful graft material due to its strength, osteoconductivity and the ease with which its pore geometry can be controlled.
Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this ...treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.
The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.
A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001 was observed with salvage chemotherapy.
When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.
This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.
A self-adjusting sensing circuit spin-torque transfer magnetic random access memory (STT-MRAM) is proposed. STT-MRAM is considered to be the most promising candidate among the new emerging memories. ...However, read performance has emerged as a new bottleneck, because of its low tunnelling magneto-resistance ratio (TMR) and low read current. The proposed self-adjusting sensing circuit shows an improved sensing margin, overcoming the weaknesses of the STT-MRAM. The proposed circuit using Verilog-A model, a 65 nm complementary metal–oxide–semiconductor process also evaluated, and Monte Carlo analysis. The results of analysis show that the proposed circuit ensures a certain sensing margin, which is more than 200 mV in TMR 150% and about 50 mV in TMR 100%.
Abstract Purpose The purpose of this study is to evaluate the correlation between lymph node count (LNC) and survival and to evaluate whether lymph node ratio (LNR) which is related to LNC is a ...better predictor of survival for gastric cancer than the N category of UICC/AJCC through a multi-institutional cohort study. Methods The study cohort included 3284 patients from eight institutions. Lower and upper quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27, and 0.49) for the LNR categories were based on Classification and Regression Trees techniques. Akaike information criteria (AIC) for Cox regression models was used to evaluate goodness of fit between competing predictor variables (LNR vs. N category). Results The 5-year disease-specific survival (DSS) rates of lower and upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN category, the upper quartile of LNC showed better survival than the lower quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0–0.06, 0.06–0.27, 0.27–0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2% respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor status, distant metastasis, and tumor differentiation significantly affected survival. The analysis also confirmed superiority of LNR compared with N category in the AIC analysis. Conclusion Higher LNC correlated with better survival in patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a better predictor of survival than N category of UICC/AJCC.
The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles ...(PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (
n=109) and in healthy controls (
n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.
There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated ...short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer.
The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days.
Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups.
Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).
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