Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study.

BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study.

BACKGROUND: One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. METHODS: A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. RESULTS: The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74-4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65-3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84-2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39-1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84-3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11-3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76-2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35-1.96, P < 0.0001; ≥ 8 cycles: 67.2%). CONCLUSIONS: Reducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer.

BACKGROUND: This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). METHODS: One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. RESULTS: In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48-0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse: 3-6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022). CONCLUSIONS: The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.

Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data.

BACKGROUND: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. METHODS: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. RESULTS: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. CONCLUSIONS: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

Early removal of central venous catheter may not impact the in-hospital mortality in patients with acute leukemia.

Central venous catheters (CVCs) are generally required for chemotherapy in patients with acute leukemia, but catheter-related infection is one of the common causes of neutropenic fever. We investigated the in-hospital mortality according to early removal of CVCs and the factors influencing the mortality in patients with acute leukemia undergoing remission induction chemotherapy. This study retrospectively analyzed the hospital record data of 278 patients with acute leukemia treated with non-tunneled CVCs and remission induction chemotherapy in a single institution. Bloodstream infection was more common (p < 0.0001) and median peak C-reactive protein (CRP) levels after neutropenic fever were significantly higher (23.3 vs. 14.5 mg/dl, p = 0.003) in the group with early removal than in the group with maintenance of the CVC. Multivariate analysis of the patients revealed a significant decrease in the mortality with female gender (odds ratio (OR): 0.19, 95% confidence interval (CI): 0.06-0.54, p = 0.002) and a significant increase in the mortality according to the peak CRP (OR 1.12, 95% CI: 1.07-1.17, p < 0.0001). By contrast, early removal of the CVC had no significant effect on the mortality (OR = 1.16, 95% CI: 0.54-2.47, p = 0.706) in univariate analysis. Furthermore, subsequent bloodstream infection after clinical decision for maintenance or early removal of the CVC was confirmed more frequently in the group with early removal (early removal, 22.6%; maintenance, 7.6%, p < 0.0001). Early removal of the CVC had no benefit regarding the mortality and prophylaxis of bloodstream infection in patients with acute leukemia undergoing remission induction chemotherapy. Therefore, maintaining a CVC for as long as possible may be considered, if catheter-related bloodstream infection is not strongly suspected.

Combination versus single-agent as palliative chemotherapy for gastric cancer.

BACKGROUND: Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. METHODS: A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). RESULTS: Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p < 0.0001, in each case). The median OS of patients who received CC was significantly longer than that of patients who received SC (11 vs. 8 months, p < 0.0001). No difference in OS between CC and SC was observed in elderly patients (p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p < 0.0001, in each case), whereas poor PS (p = 0.004), signet ring cell (p < 0.0001), peritoneal metastasis (p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. CONCLUSIONS: Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.

Treatment strategy and outcomes in locally advanced head and neck squamous cell carcinoma: a nationwide retrospective cohort study (KCSG HN13-01).

BACKGROUND: By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. METHODS: This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. RESULTS: A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24-89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). CONCLUSIONS: In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

Influence of SiC and TiC nanoparticles reinforcement on the microstructure, tribological, and scratch resistance behavior of electroless Ni-P coatings.

Two different ceramic carbide nanoparticles (SiC, and TiC) were separately incorporated into the Ni-P matrix via the electroless deposition method. As prepared Ni-P, Ni-P-SiC, and Ni-P-TiC coatings were subjected to heat treatment at 400 °C for 1 h. The surface morphology, microstructural transformation, Vicker's microhardness, tribological and scratch resistance properties were studied with reference to the different carbide reinforcements as well as heat treatment. Inter-nodular space, craters and kinks are created due to the branching effect of nodules in the surface of the Ni-P-SiC (TiC) composite coatings. After the heat treatment, the matrix phase transformation was not altered due to the incorporation of SiC or TiC into the Ni-P coating; however, a slight increase in residual stress was identified from the XRD analysis. In addition, the content of carbon deposition was found to be higher in the matrix of Ni-P-SiC composite coating than that in the Ni-P-TiC coating. The agglomeration of SiC particles was higher than TiC particles in the coating matrix, which was also supported by the result of Zeta potential measurement. Heat treatment improved wear and coefficient of friction in the Ni-P-SiC and Ni-P-TiC composite coatings. Compared to Ni-P-SiC coating, Ni-P-TiC coating revealed the enhanced tribological and scratch resistance performance after the heat treatment.

Effects of Remote Monitoring of Blood Pressure in Management of Urban Hypertensive Patients: A Systematic Review and Meta-Analysis.

Background:Remote home blood pressure monitoring (RBPM) has been shown as effective in managing hypertension in underserved areas. Effects on urban patients, who are more easily provided with high-quality medical services, are still unclear. We systematically review previously published randomized controlled trials on the effect of RBPM for urban hypertensive patients.Methods:We searched electronic databases for studies published in English up to October 2018. Studies comparing the use of RBPM to face-to-face care were included. Outcome measures were changes in office blood pressure (BP) and the rate of BP control.Results:We identified 1,433 potential references for screening, of which 27 were eligible for review. Substantial heterogeneity was evident for the investigated variables. A significant standardized mean difference (SMD) was observed for RBPM for systolic BP, but the effect size was small compared to face-to-face care and was clinically irrelevant in avoiding cardiovascular events (0.212, 95% confidence interval 0.148-0.275; p < 0.001). For diastolic BP, the SMD between the two groups was small (0.170, p < 0.001) and the effect of RBPM was irrelevant in preventing cardiovascular events. The effect on the rate of BP control was significantly high for the intervention group (relative risk: 1.136; p = 0.018).Conclusions:This review demonstrates that RBPM performed on urban hypertensive patients has limited value and seems not to be superior to ordinary care in avoidance of cardiovascular events. Further studies are needed to provide more reliable information about the effectiveness of RBPM in preventing hypertensive cardiovascular complications.

Treatment with Recombinant Human MG53 Protein Increases Membrane Integrity in a Mouse Model of Limb Girdle Muscular Dystrophy 2B.

Limb girdle muscular dystrophy type 2B (LGMD2B) and other dysferlinopathies are degenerative muscle diseases that result from mutations in the dysferlin gene and have limited treatment options. The dysferlin protein has been linked to multiple cellular functions including a Ca2+-dependent membrane repair process that reseals disruptions in the sarcolemmal membrane. Recombinant human MG53 protein (rhMG53) can increase the membrane repair process in multiple cell types both in vitro and in vivo. Here, we tested whether rhMG53 protein can improve membrane repair in a dysferlin-deficient mouse model of LGMD2B (B6.129-Dysftm1Kcam/J). We found that rhMG53 can increase the integrity of the sarcolemmal membrane of isolated muscle fibers and whole muscles in a Ca2+-independent fashion when assayed by a multi-photon laser wounding assay. Intraperitoneal injection of rhMG53 into mice before acute eccentric treadmill exercise can decrease the release of intracellular enzymes from skeletal muscle and decrease the entry of immunoglobulin G and Evans blue dye into muscle fibers in vivo. These results indicate that short-term rhMG53 treatment can ameliorate one of the underlying defects in dysferlin-deficient muscle by increasing sarcolemmal membrane integrity. We also provide evidence that rhMG53 protein increases membrane integrity independently of the canonical dysferlin-mediated, Ca2+-dependent pathway known to be important for sarcolemmal membrane repair.

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation.

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial.

BACKGROUND: The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. METHODS: CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov, NCT00411229. FINDINGS: We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54-70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51-0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group. Adverse event data were not collected after the primary analysis. INTERPRETATION: Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. FUNDING: F Hoffmann La-Roche and Sanofi.

Patterns of neutropenia and risk factors for febrile neutropenia of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age ≥65 yr, comorbidities, bone marrow involvement, and baseline serum albumin ≤3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.

Multimodal real-time imaging with laser speckle contrast and fluorescent contrast.

INTRODUCTION: Laser speckle contrast imaging (LSCI) can achieve real-time 2D perfusion maps non-invasively. However, LSCI is still difficult to use in general clinical applications because of movement sensitivity and limitations in blood flow analysis. To overcome this, fluorescence imaging (FI) is combined with LSCI using a light source with a wavelength of 785 nm in near-infrared (NIR) region and validates to visualize real-time blood perfusion. MATERIALS AND METHODS: The system was performed using Intralipid and indocyanine green (ICG) in a flow phantom that has three tubes and controlled the flow rate in 0-150 µl/min range. First, real-time LSCI was monitored and measured the change in speckle contrast by reperfusion. Then, we visualized blood perfusion of a rabbit ear under the non-invasive condition by intravenous injection using a total of five different ICG concentration solutions from 128 µM to 3.22 mM. RESULTS: The combined system achieved the performance of processing laser speckle images at about 37-38 fps, and we simultaneously confirmed the fluorescence of ICG and changes in speckle contrast due to intralipid as a light scatterer. In addition, we obtained real-time contrast variation and fluorescent images occurring in rabbit's blood perfusion. CONCLUSIONS: The aim of this study is to provide a real-time diagnostic imaging system that can be used in general clinical applications. LSCI and FI are combined complementary for observing tissue perfusion using a single NIR light source. The combined system could achieve real-time visualization of blood perfusion non-invasively.

Clinical Outcomes in Patients With DLBCL Treated With R-CHOP According to Radiotherapy and Interim PET Response.

Background/Aim: Interim positron emission tomography/computed tomography (PET/CT) scan is a valuable tool for assessing the early metabolic response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Although radiotherapy is an effective treatment for lymphoma, especially for local tumor control, the role of consolidative radiotherapy in diffuse large B-cell lymphoma (DLBCL) remains controversial. This study analyzed the clinical outcomes of patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), stratified by interim PET response and the administration of radiotherapy. Patients and Methods: We conducted a retrospective review of 107 patients with DLBCL treated with R-CHOP chemotherapy between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), and freedom from disease progression (FFDP) were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Forty-six patients were included in this analysis, with a median follow-up time of 65.9 months (range=4.7-125.3 months). The metabolic CR (mCR) group exhibited superior OS, RFS, and FFDP compared with the metabolic PR (mPR) group (p=0.003, p=0.001, and p=0.008, respectively). The 1-, 2-, and 5-year FFDP were 92.97%, 89.3%, and 85.6%, respectively, in the mCR group and 78.6%, 61.9%, and 44.2%, respectively, in the mPR group. In subgroup analysis, the FFDP of the mPR group without radiotherapy was significantly lower than that of the other groups (mCR with/without radiotherapy and mPR with radiotherapy, p=0.001). Conclusion: Consolidative radiation therapy using interim PET can benefit patients who do not achieve mCR. Further well-controlled prospective randomized trials are required.

Synthesis of recyclable and light-weight graphene oxide/chitosan/genipin sponges for the adsorption of diclofenac, triclosan, and microplastics.

Emerging micropollutants, such as pharmaceuticals and microplastics (MPs), have become a pressing water environmental concern. The aim of this study is to synthesize chitosan sponges using graphene oxide (GO) and genipin (GP) for the removal of pharmaceuticals (diclofenac (DCF) and triclosan (TCS)) and MPs, verify their adsorption mechanisms, evaluate the effects of temperature, pH, and salinity on their adsorption capacities, and determine their reusability. The GO5/CS/GP sponge exhibited a macroporous nature (porosity = 95%, density = 32.6 mg/cm3). GO and cross-linker GP enhanced the adsorption of DCF, TCS, and polystyrene (PS) MPs onto the CS sponges. The adsorption of DCF, TCS, and PS MPs involved multiple steps: surface diffusion and pore diffusion of the sponge. The adsorption isotherms demonstrated that Langmuir model was the most fitted well model to explain adsorption of TCS (qm = 7.08 mg/g) and PS MPs (qm = 7.42 mg/g) on GO5/CS/GP sponge, while Freundlich model suited for DCF adsorption (qm = 48.58 mg/g). DCF adsorption was thermodynamically spontaneous and endothermic; however, the adsorption of TCS and PS MPs was exothermic (283-313 K). The optimal pH was 5.5-7 due to the surface charge of the GO5/CS/GP sponge (pHzpc = 5.76) and ionization of DCF, TCS, and PS MPs. As the salinity increased, DCF removal efficiency drastically decreased due to the weakening of electrostatic interactions; however, TCS removal efficiency remained stable because TCS adsorption was mainly caused by hydrophobic and π-π interactions rather than electrostatic interaction. The removal of PS MPs was enhanced by the electrostatic screening effects of high Na+ ions. PS nanoplastics (average size = 26 nm) were removed by the GO5/CS/GP sponge at a rate of 73.0%, which was better than that of PS MPs (41.5%). In addition, the GO5/CS/GP sponge could be recycled over five adsorption-desorption cycles.

Facet-Controlled Growth of Hydroxyapatite for Effectively Removing Pb from Aqueous Solutions.

To address the growing concerns regarding severe water pollution, effective and environmentally friendly adsorbents must be identified. In this study, we prepared hydroxyapatite (HAp, Ca10(PO4)6(OH)2) as an eco-friendly absorbent via simple precipitation and obtained rod- (r-HAp) and plate-shaped HAp (p-HAp). The approach to obtaining p-HAp involved a low pH titration rate, promoting growth along the c-axis due to the adsorption of OH- on the (110) facet. Conversely, r-HAp was obtained by maintaining a high concentration of OH- during the initial stage through rapid pH titration, leading to a stronger restrictive effect on the growth of positively charged a(b)-planes. p-HAp demonstrated superior adsorption capacity, removing Pb through dissolution and recrystallization, achieving an impressive 625 mg/g within a 60 min reaction time compared to r-HAp. Our findings afford insights into the Pb removal mechanisms of HAp with different morphologies and can aid in the development of water purification strategies against heavy metal contamination.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

PURPOSE: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib. CONCLUSION: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

5-Fluorouracil, mitomycin-c, and polysaccharide-k versus uracil-ftorafur and polysaccharide-K as adjuvant chemoimmunotherapy for patients with locally advanced gastric cancer with curative resection.

BACKGROUND: Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer (LAGC), the optimal regimen remains to be determined. We conducted a randomized trial comparing oral (PO) chemoimmunotherapy (CITX) with intravenous (IV) CITX in LAGC patients (stages IB-IIIB) with curative resection (≥ D2 dissection). METHODS: The patients were randomized to the IV (5-fluorouracil 500 mg/m(2) weekly for 24 weeks, mitomycin-C 8 mg/m(2) every 6 weeks × 4) or the PO (uracil-ftorafur (UFT) 400-600 mg/day for 12 months) group. Patients in both groups received PO polysaccharide-K (3 g/day for 4 months). The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival. RESULTS: The trial was closed prematurely after enrolling 82 patients (44 in the IV group, 38 in the PO group). With a median follow-up of 82 months, there were no significant differences in the 5-year disease-free survival (73% vs. 55%, p = 0.358) and overall survival (77% vs. 66%, p = 0.159) between the 2 groups. The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia, thrombocytopenia, and vomiting. CONCLUSIONS: PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX, with lower toxicity in the adjuvant treatment for LAGC.