The energy calibration is performed with y rays of energy up to 9 MeV from the reaction Ni(n, y)Ni, with electrons from muon decays, and with the P decays from spallation products of cosmic-ray-muon interactions. From these calibrations, the absolute energy normalization is known to be better than 3%. The rms energy resolution for an electron is expressed by 22%/[E, /(10

Background: Nivolumab has a survival benefit for heavily pretreated patients with advanced or recurrent G/GEJ cancer. ATTRACTION-4 is a randomized, multicenter, phase 2/3 study to evaluate the efficacy and safety of nivolumab plus chemotherapy vs. chemotherapy as first-line treatment in patients with HER2-negative, advanced or recurrent G/GEJ cancer. Here we report the results of the double-blind phase III part.Methods: Patients were randomized 1:1 to receive nivolumab plus chemotherapy (N+C, S-1 plus oxaliplatin or capecitabine plus oxaliplatin) or placebo plus chemotherapy (C). Nivolumab or placebo was intravenously administered every 3 weeks until disease progression or unacceptable toxicity. Tumor assessment was performed every 6 weeks through week 54, then repeated every 12 weeks. The co-primary endpoints were centrally-assessed PFS and OS, and it was prespecified that the primary objective is deemed to be achieved if at least one of the null hypotheses of the primary endpoints is rejected.Results: A total of 724 Asian patients were randomized to N+C (n¼362) or C (n¼362) between Mar 7, 2017, and May 10, 2018. At the interim analysis primary for PFS with the median follow-up period of 11.6 mo, PFS was significantly improved in N+C vs. C (HR 0.68; 98.51% CI 0.51-0.90; p¼0.0007; median PFS, 10.5 vs. 8.3 mo), meeting the primary endpoint. At the final analysis primary for OS with the median follow-up period of 26.6 mo, there was no statistically significant difference (HR 0.90; 95% CI 0.75-1.08; p¼0.257; median OS, 17.5 vs. 17.2 mo), while PFS was continuously longer in N+C than in C. ORR was higher in N+C than in C (57.5 vs. 47.8%; p¼0.0088). The incidences of grade 3 to 5 treatment-related adverse events were 57.9% in N+C and 49.2% in C.Conclusions: PFS was significantly improved in N+C vs. C, achieving the primary objective. The combination of nivolumab and chemotherapy, which demonstrated clinically meaningful efficacy in PFS and ORR with a manageable safety profile but not statistically significant improvement in OS, can be considered a new first-line treatment option in advanced or recurrent G/GEJ cancer.

Background: T-DXd is a HER2-targeting antibodyedrug conjugate approved for pts with advanced HER2+ mBC based on the results from DESTINY-Breast01 (NCT03248492). This is the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC previously treated with trastuzumab and taxane. This is the first reported randomized study of T-DXd in BC.Methods: Pts were randomized 1:1. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response, PFS by investigator, and safety.

Hyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of CP asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams.In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hepex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW × 10 7 sec integrated proton beam power (corresponding to 1.56 × 10 22 protons on target with a 30 GeV proton beam) to a 2.5-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the CP phase δCP can be determined to better than 19 degrees for all possible values of δCP , and CP violation can be established with a statistical significance of more than 3 σ (5 σ) for 76% (58%) of the δCP parameter space.

Objectives: The purpose of this study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced or inflammatory breast cancer. Each prediction method was compared with the gold standard of surgical pathology. Methods: 43 patients (age range, 25-62 years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We compared the predicted residual tumour size and the predicted response on imaging and clinical examination with residual tumour size and response on pathology. Statistical analysis was performed using weighted kappa statistics and intraclass correlation coefficients (ICC). Conclusion:Predictions of response and residual tumour size made on MRI were better correlated with the assessments of response and residual tumour size made upon pathology than were predictions made on the basis of clinical examination, mammography or sonography. Thus, the evaluation of predicted response using MRI could provide a relatively sensitive early assessment of chemotherapy efficacy.

Background The humanized monoclonal antibody (mAb) trastuzumab (H) + chemotherapy (chemo) prolongs disease-free survival (DFS) in patients (pts) with HER2-positive breast cancer (BC) in the adjuvant setting. Vascular endothelial growth factor (VEGF-A), one central regulator of angiogenesis, is a downstream target of HER2. Tumors overexpressing HER2 also overexpress VEGF-A and exhibit increased angiogenic potential. Combining H with the anti-VEGF-A mAb bevacizumab (B) significantly decreased tumor volume vs B or H alone in HER2-positive xenograft models and demonstrated efficacy in phase 2 studies. In the phase 3 AVEREL study in pts with HER2-positive metastatic BC, adding B to H + docetaxel (T) led to a non-significant increase in a duration of PFS and objective response rates. Chemo plus H±B is now explored in this large phase 3 trial to assess the impact of VEGF-A blockade on residual or micrometastatic disease in the adjuvant setting. Methods BETH (NCT00625898) is a randomized, phase 3, open-label study evaluating the addition of B to 2 different H-chemo regimens. Pts had centrally-confirmed HER2-positive BC (FISH+ and/or IHC 3+), ECOG PS 0-1, unilateral invasive breast adenocarcinoma, total mastectomy or lumpectomy, and LVEF ≥55%. Prior therapy with anthracyclines, taxanes, carboplatin (C), H or B for any malignancy or radiotherapy, chemo, and/or targeted therapy for the currently diagnosed BC were not permitted. Pts were stratified by center, hormone receptor status (ER and/or PR-positive, ER/PR-negative), and axillary lymph node status (0, 1-3, 4+) before inclusion into 1 of 2 chemo cohorts, and then randomized. All pts were recruited by investigators from the Translational Research in Oncology (TRIO/CIRG), the National Surgical Adjuvant Breast and Bowel Project (NSABP) or a group of independent sites. Cohort 1 (3231 pts) included pts receiving 6 cycles of TCH±B followed by H±B for 1 yr after the first dose. Cohort 2 (278 pts) included pts from some independent sites electing to use anthracycline-based therapy and these pts received 3 cycles of TH±B followed by 3 cycles of 5-fluorouracil, epirubicin, cyclophosphamide followed by H±B to complete 1 yr of treatment. T was given at 8 mg/kg IV loading dose, 6 mg/kg IV q3w thereafter; B was given at 15 mg/kg IV q3w. The primary endpoint is invasive DFS (IDFS) for B-containing vs. non-B-containing regimens. Secondary endpoints are IDFS within chemo cohorts, DFS, overall survival, recurrence-free interval (RFI), distant RFI, safety including specific cardiac assessments, and the identification of predictive biomarkers for B. The sample size was determined to test the hypothesis of interest, both in the faster accruing cohort and overall. With 3509 pts enrolled, the trial will have 85% power to detect a HR of 0.70 favoring the addition of B overall, irrespective of chemo regimen. With ∼3000 pts in the faster-accruing cohort, the study will have 80% power to detect a hazard ratio (HR) of 0.70 at a 2-sided alpha of 0.05. Median duration of follow-up will be 36 months in Jun 13, cut-off date of the primary analysis. Initial efficacy, safety, and plasma marker analyses will be reported. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S1-03.

We report on measurements of the 1S, 2S and 3S di erential cross sections d 2 =dp T dy jyj 0:4 , as well as on the 1S polarization in pp collisions at p s = 1:8TeV using a sample of 77 3 pb ,1 collected by the Collider Detector at Fermilab.The three resonances were reconstructed through the decay ! + , . The measured angular distribution of the muons in the 1S rest frame is consistent with unpolarized meson production.

Background T-DM1 has improved PFS and OS in HER2+ advanced BC patients (pts) who previously progressed on trastuzumab and a taxane (Verma NEJM 2012). Preclinical data show that atezo (anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1 to restore antitumor immunity. PD-L1 is often expressed on tumor-infiltrating immune cells (IC) in BC. KATE2 (NCT02924883) is the first study to assess atezo combined with T-DM1 in previously treated HER2+ advanced BC. Method Eligible pts had HER2+ advanced BC previously treated with trastuzumab and a taxane and progressed on treatment for metastatic disease or within 6 mo of adjuvant therapy. Pts were randomized 2:1 to atezo 1200 mg or pbo+T-DM1 3.6 mg/kg IV q3w (crossover not permitted). The primary endpoint was investigator-assessed PFS per RECIST v1.1. Additional endpoints included OS, ORR, DoR (secondary), PFS in the PD-L1+ subgroup (exploratory) and safety. Data cutoff: 11 Dec 2017. Result 133 pts were randomized to atezo+T-DM1 and 69 pts to pbo+T-DM1. 49% and 46% received prior pertuzumab for metastatic BC; median duration of pertuzumab treatment was 10 and 13 mo, respectively. Median follow-up was 8.5 and 8.4 mo, respectively. Efficacy in the ITT population and biomarker subgroups are shown. PFS HR was 0.82 (95% CI: 0.55, 1.23); p=0.3332. At data cutoff, 13 OS events (10%) in the atezo+T-DM1 arm and 8 (12%) in the pbo+T-DM1 arm had occurred. mDoR was not reached. 44% and 41% of safety-evaluable pts had an AE of Gr ≥3 with atezo+T-DM1 and pbo+T-DM1, respectively. The most common was thrombocytopenia (13% and 4%). The incidence of serious AEs (SAEs) was 33% with atezo+T-DM1 and 19% with pbo+T-DM1, with the most common being Gr 1-2 pyrexia with atezo+T-DM1 (5%) and abdominal pain (3%) and seizure (3%) with pbo+T-DM1. AE rates leading to atezo/pbo or T-DM1 discontinuation were 25% and 15%, respectively, with atezo+T-DM1 and 15% and 13% with pbo+T-DM1. 1 patient in the atezo+T-DM1 arm had a drug-related Gr 5 AE (hemophagocytic syndrome). ITT and Biomarker Subgroups: Efficacy Atezo+T-DM1 (n=133)Pbo+T-DM1 (n=69)mPFS, mo8.26.86-mo PFS, %585112-mo PFS, %3834ORR, %a4543CR67PR3936PD-L1 IHCb PD-L1+PD-L1-PD-L1+PD-L1-Patients, n57762742mPFS, mo8.56.84.18.2ORR, %a54403350Stromal TILsc TIL-high (≥5%)TIL-low (<5%)TIL-high (≥5%)TIL-low (<5%)Patients, n80454025mPFS, mo8.55.55.3NAORR, %a48383848HER2c IHC3+IHC0-2+IHC3+IHC0-2+Patients, n103305613mPFS, mo8.55.98.04.0ORR, %a52234631aORR-evaluable pts (measurable disease at baseline): n=132 in atezo+T-DM1 arm. bPD-L1+, IC1/2/3; PD-L1–, IC0; measured per the VENTANA SP142 IHC assay. cPost hoc exploratory analyses. Conclusion Atezo+T-DM1 did not demonstrate a clinically significant PFS benefit vs pbo+T-DM1; OS and DoR data are not yet mature. Numerically higher PFS and ORR were seen with atezo+T-DM1 in PD-L1+ pts. T-DM1 safety in both arms was consistent with its known profile. Although the combination of atezo+T-DM1 showed a numerically higher incidence of SAEs and discontinuation of atezo due to an AE, rates of Gr 3-5 AEs were similar between arms. Additional biomarker data, including gene expression and mutation data, will be presented. Citation Format: Emens LA, Esteva F, Beresford M, Saura C, De Laurentiis M, Kim S-B, Im S-A, Patre M, Wang Y, Mani A, Liu H, de Haas S, Loi S. Results from KATE2, a randomized phase 2 study of atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-01.