Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial.

BACKGROUND: Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy. PATIENTS AND METHODS: From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety. RESULTS: Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001). CONCLUSIONS: Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option. CLINICAL TRIAL INFORMATION: UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

REVERCE: a randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients.

BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.

Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

Background: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Patients and methods: Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Results: Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. Conclusions: The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. Registered clinical trial number: UMIN000010507.

A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer.

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).

Thermally Assisted Nonvolatile Memory in Monolayer MoS2 Transistors.

We demonstrate a novel form of thermally-assisted hysteresis in the transfer curves of monolayer MoS2 FETs, characterized by the appearance of a large gate-voltage window and distinct current levels that differ by a factor of ∼102. The hysteresis emerges for temperatures in excess of 400 K and, from studies in which the gate-voltage sweep parameters are varied, appears to be related to charge injection into the SiO2 gate dielectric. The thermally-assisted memory is strongly suppressed in equivalent measurements performed on bilayer transistors, suggesting that weak screening in the monolayer system plays a vital role in generating its strongly sensitive response to the charge-injection process. By exploiting the full features of the hysteretic transfer curves, programmable memory operation is demonstrated. The essential principles demonstrated here point the way to a new class of thermally assisted memories based on atomically thin two-dimensional semiconductors.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863.

A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.

BACKGROUND: Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. PATIENTS AND METHODS: The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. RESULTS: Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death. CONCLUSIONS: In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.

Multicentre analysis of long-term outcome after surgical resection for gastric cancer liver metastases.

BACKGROUND: The efficacy of surgical resection for gastric cancer liver metastases (GCLMs) is currently debated. Hitherto, no large-scale clinical studies have been conducted. METHODS: This retrospective multicentre study analysed a database of consecutive patients with either synchronous or metachronous metastases who underwent surgical R0 resection for GCLM between 1990 and 2010. Clinical data were collected from five cancer centres in Japan. Survival curves were assessed, and clinical parameters were evaluated to identify predictors of prognosis. RESULTS: A total of 256 patients were enrolled. The mean(s.d.) number of hepatic tumours resected was 2.0(2.4). The surgical mortality rate was 1.6 per cent. Median follow-up was 65 (range 1-261) months. Recurrences were detected in 192 patients (75.0 per cent). The median interval from hepatic resection to recurrence was 7 (range 1-72) months, and the dominant site of recurrence was the liver (72.4 per cent). Actuarial 1-, 3- and 5-year overall and recurrence-free survival rates were 77.3, 41.9 and 31.1 per cent, and 43.6, 32.4 and 30.1 per cent, respectively. Median overall and recurrence-free survival times were 31.1 and 9.4 months respectively. Multivariable analysis identified serosal invasion of the primary gastric cancer (hazard ratio (HR) 1.50; P = 0.012), three or more liver metastases (HR 2.33; P < 0.001) and liver tumour diameter at least 5 cm (HR 1.62; P = 0.005) as independent predictors of poor survival. CONCLUSION: Clinically resectable GCLM is rare, but strict and careful patient selection can lead to long-term survival following R0 surgical resection.

Randomized clinical trial of skin closure by subcuticular suture or skin stapling after elective colorectal cancer surgery.

BACKGROUND: The best suture method to prevent incisional surgical-site infection (SSI) after clean-contaminated surgery has not been clarified. METHODS: Patients undergoing elective colorectal cancer surgery at one of 16 centres were randomized to receive either subcuticular sutures or skin stapling for skin closure. The primary endpoint was the rate of incisional SSI. Secondary endpoints of interest included time required for wound closure, incidence of wound problems, postoperative length of stay, wound aesthetics and patient satisfaction. RESULTS: A total of 1264 patients were enrolled. The cumulative incidence of incisional SSI by day 30 after surgery was similar after subcuticular sutures and stapled closure (8·7 versus 9·8 per cent respectively; P = 0·576). Comparison of cumulative incidence curves revealed that SSI occurred later in the subcuticular suture group (P = 0·019) (hazard ratio 0·66, 95 per cent c.i. 0·45 to 0·97). Wound problems (P = 0·484), wound aesthetics (P = 0·182) and postoperative duration of hospital stay (P = 0·510) did not differ between the groups; subcuticular sutures took 5 min longer than staples (P < 0·001). Patients in the subcuticular suture group were significantly more satisfied with their wound (52·4 per cent versus 42·7 per cent in the staple group; P = 0·002). CONCLUSION: Compared with skin stapling, subcuticular sutures did not reduce the risk of incisional SSI after colorectal surgery. REGISTRATION NUMBER: UMIN000004001 (http://www.umin.ac.jp/ctr).

Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma.

BACKGROUND: Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors. METHODS: Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. RESULTS: Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. CONCLUSION: Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy.

Pathogenicity of exopolysaccharide-producing Actinomyces oris isolated from an apical abscess lesion.

AIM: To demonstrate a capacity for producing exopolysaccharides (EPSs) and an ability to form biofilm on abiotic materials of Actinomyces oris strain K20. METHODOLOGY: The productivity of EPSs and the ability to form biofilm of strain K20 were evaluated by measuring viscosity of spent culture media and by scanning electron microscopy (SEM) and the biofilm assay on microtitre plates, respectively. High-performance liquid chromatography was used to determine the chemical composition of the viscous materials. To examine the role of the viscous materials attributable to the pathogenicity in this organism, the ability of strain K20 to induce abscess formation was compared in mice to that of ATCC 27044. RESULTS: The viscosity of the spent culture media of K20 was significantly higher than that of ATCC 27044. Strain K20 showed dense meshwork structures around the cells and formed biofilms on microtitre plates, whereas ATCC 27044 did not. Chemical analysis of the viscous materials revealed that they were mainly composed of neutral sugars with mannose constituting 77.5% of the polysaccharides. Strain K20 induced persistent abscesses in mice lasting at least 5 days at a concentration of 10(8) cells mL(-1), whereas abscesses induced by ATCC 27044 healed and disappeared or decreased in size at day 5. CONCLUSIONS: Strain K20 produced EPSs, mainly consisting of mannose, and formed biofilms. This phenotype might play an important role for A. oris to express virulence through the progression of apical periodontitis.

Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.

Hirschsprung disease (HSCR) is sometimes associated with a set of characteristics including mental retardation, microcephaly, and distinct facial features, but the gene mutated in this condition has not yet been identified. Here we report that mutations in SIP1, encoding Smad interacting protein-1, cause disease in a series of cases. SIP1 is located in the deleted segment at 2q22 from a patient with a de novo t(2;13)(q22;q22) translocation. SIP1 seems to have crucial roles in normal embryonic neural and neural crest development.

Scoring tools to identify TB patients facing catastrophic costs in the Philippines.

BACKGROUND: This study was to meet a practical need to design a simple tool to identify TB patients who may potentially be facing catastrophic costs while seeking TB care in the public sector. Such a tool may help prevent and address catastrophic costs among individual patients. METHODS: We used data from the national TB patient cost survey in the Philippines. We randomly allocated TB patients to either the derivation or validation sample. Using adjusted odds ratios (ORs) and ß coefficients of logistic regression, we developed four scoring systems to identify TB patients who may be facing catastrophic costs from the derivation sample. We validated each scoring system in the validation sample. RESULTS: We identified a total of 12 factors as predictive indicators associated with catastrophic costs. Using all 12 factors, the ß coefficients-based scoring system (area under the curve [AUC] 0.783, 95% CI 0.754-0.812) had a high validity. Even with seven selected factors with OR > 2.0, the validity remained in the acceptable range (ß coefficients-based: AUC 0.767, 95% CI 0.737-0.798). CONCLUSION: The ß coefficients-based scoring systems in this analysis can be used to identify those at high risk of facing catastrophic costs due to TB in the Philippines. Operational feasibility needs to be investigated further to implement this in routine TB surveillance.

CONTEXTE: Cette étude visait à répondre à un besoin pratique de concevoir un outil simple pour identifier les patients atteints de TB qui pourraient potentiellement être confrontés à des coûts catastrophiques lorsqu'ils recherchent des soins de TB dans le secteur public. Un tel outil pourrait aider à prévenir et à traiter les coûts catastrophiques chez les patients individuels. MÉTHODES: Nous avons utilisé des données de l'enquête nationale sur les coûts des patients atteints de TB aux Philippines. Nous avons réparti aléatoirement les patients atteints de TB dans l'échantillon de dérivation ou de validation. À l'aide des odds ratio (OR) ajustés et des coefficients ß de la régression logistique, nous avons développé quatre systèmes de notation pour identifier les patients atteints de TB qui pourraient être confrontés à des coûts catastrophiques à partir de l'échantillon de dérivation. Nous avons validé chaque système de notation dans l'échantillon de validation. RÉSULTATS: Nous avons identifié un total de 12 facteurs en tant qu'indicateurs prédictifs associés à des coûts catastrophiques. En utilisant les 12 facteurs, le système de notation basé sur les coefficients ß (aire sous la courbe [AUC] 0,783 ; IC 95% 0,754­0,812) avait une validité élevée. Même avec sept facteurs sélectionnés avec OR > 2,0, la validité est restée dans la plage acceptable (basée sur les coefficients ß : AUC 0,767 ; IC 95% 0,737­0,798). CONCLUSION: Les systèmes de notation basés sur les coefficients ß dans cette analyse peuvent être utilisés pour identifier les personnes à haut risque de faire face à des coûts catastrophiques liés à la TB aux Philippines. La faisabilité opérationnelle doit être étudiée plus avant pour mettre en œuvre cela dans la surveillance de routine de la TB.

Development of visible light tomographic imaging system for field-reversed configuration collisional merging experiment.

A visible light tomographic imaging system has been developed for the collisional merging experiment of field-reversed configurations (FRCs) on the FRC Amplification via Translation-Collisional Merging device at Nihon University. Two FRCs formed by field-reversed theta-pinch translate at super-Alfvénic velocity and collide with each other. The translation and collision processes are completed in 20-30 µs, and a single FRC is reformed in ∼70 µs. To study these translation and collisional merging processes, the tomographic system, including fast response tomographic cameras and a reconstruction method assuming a Rigid-Rotor (RR) model, is developed. The developed tomographic cameras simply consist of 16 channels of multi-anode photomultipliers, a band-pass filter, a slit, and a cylindrical lens, which expands the viewing angle. Because the viewing angle is limited by the size of the viewports of the metal chamber, the iterative method assuming the RR model has been applied to reconstruct tomographic images from a small number of projections. The developed tomographic imaging system can estimate the behavior of FRCs. Four cameras are installed in the two cross sections near the collision point. The radial shift of each translated FRC can be calculated by this system. Details of the developed tomographic camera system and RR reconstruction method are reported.

Search for the rare decays K(L)→π0π0µ+µ- and K(L)→π0π0X0→π0π0µ+µ-.

The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)µ(+)µ(-) and K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-), where the X(0) is a possible new neutral boson that was reported by the HyperCP experiment with a mass of (214.3 ± 0.5) MeV/c(2). We find no evidence for either decay. We obtain upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)µ(+)µ(-)) < 9.2 × 10(-11) at the 90% confidence level. This result rules out the pseudoscalar X(0) as an explanation of the HyperCP result under the scenario that the dsX(0) coupling is completely real.

Erlotinib plus bevacizumab vs erlotinib monotherapy as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer: Survival follow-up results of the randomized JO25567 study.

OBJECTIVES: The JO25567 randomized Phase II study demonstrated a statistically significant progression-free survival (PFS) benefit with erlotinib plus bevacizumab compared with erlotinib monotherapy in chemotherapy-naïve Japanese patients with epidermal growth factor receptor mutation-positive (EGFR+) non-small-cell lung cancer (NSCLC). Here we present updated PFS and final overall survival (OS) data after a median follow-up of 34.7 months. MATERIALS AND METHODS: Patients with stage IIIB/IV or postoperative recurrent NSCLC were randomized to receive oral erlotinib 150 mg once daily (n = 77) or erlotinib in combination with intravenous bevacizumab 15 mg/kg every 21 days (n = 75) until disease progression or unacceptable toxicity. OS was analyzed using an unstratified Cox proportional hazards model. RESULTS: Consistent with the primary analysis, addition of bevacizumab to erlotinib was associated with a significant improvement in PFS (hazard ratio [HR] 0.52; 95 % confidence interval [CI]: 0.35-0.76; log-rank two-sided P = 0.0005; median 16.4 months vs 9.8 months, respectively). In contrast, a significant improvement in OS was not seen (HR 0.81; 95 % CI, 0.53-1.23; P =  0.3267; median 47.0 months vs 47.4 months, respectively). Post-study therapy was similar between the treatment arms and EGFR mutation type did not affect OS outcomes. The 5-year OS rate was numerically higher with erlotinib plus bevacizumab vs erlotinib monotherapy (41 % vs 35 %). Updated safety analyses confirmed the previously reported manageable tolerability profile, with no new safety issues. CONCLUSION: Addition of bevacizumab to first-line erlotinib did not show significant improvement in OS in Japanese patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC. Both treatment arms showed a similar median OS benefit (as long as 4 years), irrespective of individual patient characteristics. Results from ongoing studies evaluating the combination of EGFR and VEGF signaling inhibitors are eagerly awaited. TRIAL REGISTRATION: JapicCTI-111390 and JapicCTI-142569.

Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study.

BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.

The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment.

Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus-induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.