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Although radiation therapy is one of the most significant treatment modalities for localized prostate cancer, the prognostic factors for biochemical recurrence (BCR) regarding the treatment plan are unclear. We aimed to develop a novel dosiomics-based prediction model for BCR in patients with prostate cancer and clarify the correlations between the dosimetric factors and BCR.This study included 489 patients with localized prostate cancer (BCR: 96; no-BCR: 393) who received intensity modulated radiation therapy. A total of 2475 dosiomic features were extracted from the dose distributions on the prostate, clinical target volume (CTV), and planning target volume. A prediction model for BCR was trained on a training cohort of 342 patients. The performance of this model was validated using the concordance index (C-index) in a validation cohort of 147 patients. Another model was constructed using clinical variables, dosimetric parameters, and radiomic features for comparisons. Kaplan-Meier curves with log-rank analysis were used to assess the univariate discrimination based on the predictive dosiomic features.The dosiomic feature derived from the CTV was significantly associated with BCR (hazard ratio, 0.73; 95% CI, 0.57-0.93; P = .01). Although the dosiomics model outperformed the dosimetric and radiomics models, it did not outperform the clinical model. The performance significantly improved by combining the clinical variables and dosiomic features (C-index: 0.67; 95% CI, 0.65-0.68; P.0001). The predictive dosiomic features were used to distinguish high-risk and low-risk patients (P.05).The dosiomic feature extracted from the CTV was significantly correlated with BCR in patients with prostate cancer, and the dosiomics model outperformed the model with conventional dose indices. Hence, new metrics for evaluating the quality of a treatment plan are warranted. Moreover, further research should be conducted to determine whether dosiomics can be incorporated in a clinical workflow or clinical trial.

This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan–Meier method. A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p

Background Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. Methods This study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable. Results In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203). Conclusion The effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression., The real‐world benefit of combination CDK4/6 inhibitor and endocrine therapy is similar to that reported in clinical trials. Treatment‐related neutropenia, assessed by absolute neutrophil count (ANC), may be correlated with lower risk of disease progression and a lower ANC threshold for dose reduction may be warranted.

We investigated the prognostic ability of tumor subtype for patients with breast cancer brain metastases (BCBM) treated with stereotactic radiation (SRT). This is a retrospective review of 181 patients who underwent SRT to 664 BCBM from 2004 to 2019. Patients were stratified by subtype: hormone receptor (HR)-positive, HER2-negative (HR+/HER2−), HR-positive, HER2-positive (HR+/HER2+), HR-negative, HER2-positive (HR−/HER2+), and triple negative (TN). The Kaplan–Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of SRT. Multivariate analysis (MVA) was conducted using the Cox proportional hazards model. Median follow up from SRT was 11.4 months. Of the 181 patients, 47 (26%) were HR+/HER2+, 30 (17%) were HR−/HER2+, 60 (33%) were HR+/HER2−, and 44 (24%) were TN. Of the 664 BCBMs, 534 (80%) received single fraction stereotactic radiosurgery (SRS) with a median dose of 21 Gy (range 12–24 Gy), and 130 (20%) received fractionated stereotactic radiation therapy (FSRT), with a median dose of 25 Gy (range 12.5–35 Gy) delivered in 3 to 5 fractions. One-year LC was 90%. Two-year DIC was 35%, 23%, 27%, and 16% (log rank, p = 0.0003) and 2-year OS was 54%, 47%, 24%, and 12% (log rank, p

Purpose The purpose of this study was to identify the time to achieve a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL and the related factors to achieve this goal. Materials and Methods We retrospectively reviewed 2218 Japanese prostate cancer patients who received 125I brachytherapy with or without external beam radiotherapy between 2003 and 2013 at one institution. Among them, patients followed up for ≥72 months and without luteinizing hormone–releasing hormone (LH-RH) agonist/antagonist were included (total of 1089 patients). The time to a PSA nadir of ≤0.2 ng/mL (months) was defined as the time between the date of implantation and the first time the lowest PSA value reached ≤0.2 ng/mL. Biochemical recurrence (BCR) was determined using the Phoenix definition. Multivariate linear regression analysis was performed to detect the related factors to achieve this nadir. Results We assigned 409, 592, and 88 patients to the low-, intermediate-risk, and high-risk groups, respectively. The median followup time was 9.5 years. The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 (95% confidence interval: 42.3–45.7) months. The percentage of patients that achieved the nadir was 89.1%. BCR was noted in 107 (9.8%) patients. In the multivariate analysis of patients without BCR, younger age, larger prostate volume at implantation, higher initial PSA level, and monotherapy were significantly associated with longer time to achieve the PSA nadir. Conclusion The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 months. Some patients, however, may require a lengthy period of time to do so.

El COVID-19 es una enfermedad respiratoria causada por el coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2), la cual se presenta con un espectro clínico variado. En los casos moderados y graves puede asociarse con una coagulopatía que puede progresar hacia complicaciones trombóticas y coagulación vascular diseminada (CID) potencialmente fatal. En una primera fase (enfermedad moderada) la coagulopatía se manifiesta con aumento del fibrinógeno y del dímero D y en una segunda fase (enfermedad grave) como una CID con trombocitopenia, alargamiento del tiempo de protrombina y del tiempo parcial de protrombina, disminución del fibrinógeno y aumento marcado del dímero D. Con base en lo anterior se recomienda la tromboprofilaxis con heparina de bajo peso molecular o heparina no fraccionada durante la hospitalización y su continuación en el período de convalecencia en casa.

Background: Combination of a CDK4/6 inhibitor plus endocrine therapy has been shown to significantly improve the progression free survival (PFS) in patients with hormone-receptor (HR)+, HER2- metastatic breast cancer. The aims of this retrospective study was: 1) to evaluate the real-world benefit of palbociclib plus endocrine therapy as the first line treatment in HR+, HER2- metastatic breast cancer (mBC) and 2) to correlate efficacy of the combination with neutropenia (which is a common toxicity of CDK4/6 inhibitors). Methods: This study included HR+, HER2- advanced mBC patients who were treated with palbociclib plus an endocrine therapy (mainly letrozole) at Moffitt Cancer Center between January 1, 2015 and March 1, 2018. The PFS was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were investigated using the univariable and multivariable Cox models. Results: A total of 165 patients were included in this retrospective cohort study. The median PFS of the full cohort was 24.19 months (95% CI 18.93 to not reached). For patients with bone metastasis only (n = 54), the median PFS was not reached (95% CI 18.21 to not reached). For patients with non-bone-only metastasis (n = 111), the median PFS was 24.19 months (95% CI 16.33 to 33.82). Patients with higher absolute neutrophil counts (ANC) are at high risk of disease progression (HR 1.15; 95% CI 1.03 to 1.29, p = 0.013). We did not find a significant association between the value of NLR and the risk of disease progression (HR 1.07 95% 0.97 to 1.18, p = 0.203). Both ANC and NLR were used as a time dependent variable. Conclusion:The effectiveness of palbociclib plus letrozole in the treatment of HR+, HER2- metastatic breast cancer in the real-world setting was found to be similar to the results from the PALOMA-2 trial. In addition, patients with a higher ANC were found to have a higher risk for early disease progression. This has implication for clinical practice [i.e., frequent dose delay and/or dose reduction based on ANC threshold of 1000/uL may not be an optimal approach. Since infection is rare, it is reasonable to reduce this threshold to a lower level such as 750-800/uL]. Citation Format: Dakota Jenneman, Xiaojun Zhong, Junjie Ma, Weihong Sun, Heather Han, Hatem Soliman, Loretta Loftus, Ricardo Costa, Avan Armaghani, Aixa Soyano, Brian Czerniecki, M. Catherine Lee, John Kiluk, Nazanin Khakpour, Susan Hoover, Christine Laronga, Hung T Khong. Real-world benefit of CDK4/6 inhibitor and endocrine therapy combination in metastatic breast cancer and correlation with neutropenia [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-03.

Background:Patients with breast cancer brain metastases represent a poor prognosis cohort with a high unmet clinical need. Standard-of-care treatments for patients with breast cancer brain metastases include local treatments, such as surgical resection and radiation treatment modalities that include stereotactic radiosurgery (SRS) or whole brain radiotherapy. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with nivolumab and SRS will be feasible and well tolerated and may improve intracranial tumor control rates compared to SRS alone. Trial Design:The study is designed as a prospective, single-arm, nonrandomized, open-label, phase Ib trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Treatment will be initiated with a dose of nivolumab (480 mg IV) that will be repeated every 4 weeks. The initial dose of nivolumab will be followed 1 week later by SRS at sites of brain metastases or post-operative cavities. Patients will be allowed to continue endocrine and HER2-targeted therapies if brain metastases progression was noted on these agents.Eligibility:Eligible patients include those ≥18, ECOG ≤2 with ≤10 breast cancer brain metastases of all subtypes eligible for stereotactic radiation. Specific Aims:The primary objective is to evaluate the safety and feasibility of nivolumab and SRS to sites of brain metastases. Secondary objectives include evaluation of intracranial progression free survival (PFS), extracranial PFS, overall survival, local control, and distant brain control. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit.Statistical Methods:Safety and feasibility will be monitored by a 3 + 3 design followed by a dose expansion phase. Patient Accrual:This study is open with 4 patients enrolled at the time of submission. A total of 12 patients will be enrolled.Contact Information:Kamran A. Ahmed MD, Moffitt Cancer Center, email: kamran.ahmed@moffitt.org, Clinical trial information: NCT03807765. Citation Format: Kamran A Ahmed, Youngchul Kim, Avan J. Armaghani, John A. Arrington, Jimmy J. Caudell, Ricardo L. Costa, Brian J. Czerniecki, Arnold B. Etame, Peter A. Forsyth, Hung T. Khong, Sungjune Kim, Loretta Loftus, Timothy J. Robinson, Marilin Rosa, Solmaz Sahebjam, Hatem H. Soliman, Aixa E. Soyano, Nam D. Tran, H. Michael Yu, Hyo S. Han. Phase Ib study of stereotactic radiation and nivolumab in the management of metastatic breast cancer with brain metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-10-01.

Purpose Estrogen receptor–positive (ER+) breast cancer (BC) is a heterogeneous disease with an ongoing debate regarding the optimal cutoff point for clinically relevant ER expression. We used a real-world database to assess prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. Methods We used a nationwide electronic health record– (EHR-) derived deidentified database. Descriptive statistics were used to evaluate the correlation between ER expression, tumor characteristics, and treatment patterns among patients with early-stage BC. We used Kaplan-Meier survival curves to estimate relapse-free survival (RFS) and overall survival (OS). To assess an optimal ER expression level cut point, correlations between ER+ expression and clinical outcomes were performed. Results Among 4697 patients with early-stage BC, 83 (1.76%) had ER+-low BC (ER expression, 1%-9.99%), and 36 (0.8%) had ER+-intermediate BC (10%-19.9%). ER+-low tumors were associated with higher tumor grade, larger size and higher axillary tumor burden than ER+-high tumors (≥ 20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC; 21%) and ER+-low BC (22%) than ER+-high tumors (8%). Patients with ER+-low and ER+-intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER+-high tumors (P +-low or ER+-intermediate BCs. Further tumors with

Purpose: Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease. Methods and Materials: This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors. Results: Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%. Conclusions: The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

Background There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer. Methods We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed. Results The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24–154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2–3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity. Conclusions Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.

Purpose To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy. Methods Retrospective chart review of one patient. Results A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 x 3.3 x 1.9 mm. On optical coherence tomography, the egg-like structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through 8 months follow-up. The other metastatic lesions responded well to therapy. Conclusion We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.

Objectives: The aims of this study were 1) to elucidate the relationship between social capital and health by ward in Tomi City, Nagano Prefecture, in order to clarify the regional social resources available to support long-term care prevention utilizing self- and mutual support of regional residents and 2) to comprehensively investigate the activation of regional networks. Materials and Methods: We analyzed elderly (aged 65 years or older) individual survey data from 7,199 residents from all wards within Tomi City in 2014 (number of valid responses: 5,546; valid response rate: 77.0%). The social capital indicators used for the analysis included participation in community activities, regional managerial position experience, and general trust. The health indicators included self-rated mental health, activities of daily living, and depression. Standards for a "good" result for each indicator were established, and the percentages of each were tallied up by ward. Spearman's rank correlation coefficient and principal component analysis were used to investigate correlations between social capital and health. Results: The results for overall respondents indicated correlations between participation in sports and hobbies and activities of daily living (p

Purpose To compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and Materials A total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. Results The median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. Conclusions Dose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Since the University of Tokyo Atacama Observatory (TAO) is located in extremely high altitude (5,640 m.a.s.l.), safety management is one of the most important issues for the project. We have developed safety management program for work at the site in order to prevent medical illness for humans. In this program all staff have to take medical examinations such as Electrocardiogram and Hipobaria before their work starts. The results are reviewed by medical doctor. Only authorized staff can be permitted to work at the site. During stay in site, all staff need to always use oxygen supply because there is only half of the oxygen at the site. It is also important to understand physical workload at the site. Our safety staff reviews it and determines necessary resting time for each worker, e.g. great load works need to work 50 minutes and rest 10 minutes. In addition to low air pressure, very low temperature, extremely high UV radiation, and extremely dry atmosphere should be concerned. Our program requests all staff to use winter clothes, sunblock and UV protection sunglasses and a lot of potable water consumption. Keep communication is also very important to secure the safety. Normal telephone communication is not available as well as internet connectivity. We have established satellite communication as well as UHF internal communication for general works and safety coordination with other observatories in Atacama area.

The telescope of the University of Tokyo Atacama Observatory has a primary mirror with a diameter in 6.5m. In order to fabricate the reflecting film initially on the mirror surface and to maintain its optical performance over a long period, a mirror{coating facility will be installed in operation building beside enclosure of the telescope at the summit of Co. Chajnantor (5,640m). The facility consists of mirror coating chamber, cleaning unit for stripping off the old film and clean-up the mirror, and a cart with a lifter for handling the primary mirror cell. Almost all equipment, including the main chamber, was completed by early 2020 and engaged as a mirror coating facility. In order to optimize the coating parameters, comprehensive performance tests were carried out (without primary mirror cell which plays a role of a part of chamber). The evaluation items are how long it takes to reach the target vacuum level and parameters of the current, voltage, and application time during ion bombardment and aluminization. Through iterating test, we were able to obtain each parameter that ultimately met the requirements of the TAO telescope mirror.

The University of Tokyo Atacama Observatory Project is to construct a 6.5 m infrared-optimized telescope at the summit of Co. Chajnantor (5640 m altitude) in northern Chile. The telescope optics uses a Ritchey-Chretien type layout, with an under-sized secondary mirror to reduce stray light caused by thermal emission from the telescope structure. The primary mirror is a F/1.25 lightweight borosilicate glass (Ohara E6) mirror with honeycomb structure, which is developed by Steward Observatory Richard F. Caris Mirror Lab. The telescope has two Nasmyth foci and two folded-Cassegrain foci, which can be switched by rotating a tertiary mirror. The final focal ratio is 12.2 with a field of view of 25 arcmin in diameter. The telescope mount is a tripod-disk alt-azimuth mount. Both the azimuth and elevation axes are supported by and run on hydrostatic bearings, and they are driven by friction drives with servo motors, which are controlled by the telescope control system. It also controls the hexapod mount of the secondary mirror and the pneumatic actuators of the primary mirror support to keep good image quality during the observation. An off-axis Shack-Hartmann sensor installed in each focus measures the wavefront aberration of the telescope optics, then the misalignment between the secondary and primary mirrors is corrected by adjusting the hexapod mount while other aberrations are corrected by the deformation of the primary mirror. The force distribution of the actuators for correction will be calculated by fitting the wave-front errors with a series of bending modes of the primary mirror.

Institute of Astronomy, Graduate School of Science, the University of Tokyo is promoting the University of Tokyo Atacama Observatory Project, which is to construct an infrared-optimized 6.5m telescope at the summit of Co. Chajnantor (5640m altitude) in northern Chile. The high altitude and dry climate (PWV-0.5mm) realize transparent atmosphere in the infrared wavelength. The project is now approaching the final phase of the construction. Production of major components are almost completed: Production and preassembly test of a telescope mount and dome enclosure have been completed in Japan, and they are being transported to Chile. Three mirrors, the 6.5m primary, 0.9m secondary, and 1.1m-0.75m tertiary mirrors and their support systems have been all completed and tested in the USA. An aluminizing chamber have been fabricated in China, and its tests have been carried out in Japan. Development of two facility instruments, SWIMS and MIMIZUKU, are also completed. They were transported to the Subaru telescope, successfully saw the first light in 2018, and are confirmed to have the performance as designed. On-site construction work at the summit is now underway. Expansion of a summit access road from the ALMA concession was completed in 2019. Installation of foundation will follow, and then erection of the dome enclosure and a control building. The construction works are delayed by COVID-19, and we expect to complete the dome enclosure by Q3 of 2021. The telescope will be installed inside the dome and see the engineering first light by early 2022.

Background Treatment of non‐small‐cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. Methods The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. Results A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow‐up and OS for all patients were 11.8 months (range: 0‐133.6 months) and 13.1 months (95% CI: 13.08‐13.17), respectively. Median OS improved significantly for those diagnosed in 2010‐2013 (14.8 months [95% CI: 14.7‐14.9]) as compared to 2004‐2009 (12.4 months [95% CI: 12.3‐12.5]) (P

A subset of marginal zone lymphoma (MZL) has an aggressive clinical course and role of allogeneic hematopoietic cell transplant (allo-HCT) is not well defined for these patients. MZL includes three...

Neuroendocrine tumors (NETs) are rare malignancies that usually arise from the digestive tract or lungs. Metastases of NETs to the heart (epicardium) are a rare complication. We present a case of a metastatic NET involving the epicardium.

Purpose We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. Methods and Materials The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. Results Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively. Conclusions Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.

PURPOSE/OBJECTIVE(S) Radiotherapy is one of the main treatment strategies for localized prostate cancer. Although several patients receive external radiotherapy, the relationships between dosimetric factors related to the treatment planning and biochemical recurrence (BCR) remain unclear. The aims of the present study were to develop a prediction model for BCR by integrating dose-based radiomics (dosiomics) features and clinical variables in prostate cancer patients, and to clarify the relationships between the dosimetric factors and BCR. MATERIALS/METHODS A total of 489 patients with adenocarcinoma of the prostate who had been prescribed a dose of 78 Gy in 39 fractions with intensity modulated radiation therapy from 2007 to 2014 were retrospectively enrolled. A total of 2,475 dosiomic features were calculated from the 3D doses in prostate, clinical target volume (CTV), and planning target volume (PTV), and relevant 8 clinical variables for BCR were also considered. Feature selection was performed to eliminate redundant or not significant features. Multivariate cox proportional hazards regression model was trained on the training cohort of 342 patients using the selected features, and the predictive performance was validated on the validation cohort of 147 patients using the concordance index (C-index). Kaplan-Meir curves with log-rank analysis was used to assess the univariate discrimination of freedom from biochemical failure (FFBF) between high- and low-risk BCR groups. RESULTS A total of 96 patients developed BCR with the median time of 55.2 months. Two dosiomic features (1 from CTV and 1 from PTV) and three clinical variables were selected as predictive factors. Of the five, CTV (HGLRE) (hazard ratio [HR]: 0.73; 95% confidence intervals [CI]: 0.57-0.93; P = 0.01), pretreatment prostate-specific antigen (HR: 1.27; 95% CI: 1.04-1.55; P = 0.02) and positive biopsy core rate (HR: 1.40; 95% CI: 1.07-1.82; P = 0.01), were significantly associated with BCR. The C-index of the model in the validation cohort was 0.67 (95% CI: 0.65-0.68). CTV_wavelet-HHH_glrlm_HGLRE could significantly distinguish the patients into high- and low-risk groups (8-year FFBF: 76.6% vs. 87.5%, P < 0.01). CONCLUSION The dosiomic feature extracted from CTV can be a relevant predictive factor for BCR after radiotherapy in prostate cancer patients and may be useful as new metric for evaluating the quality of a treatment plan, instead of conventional dose indices.

Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of ≥10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02;P=.87). Up to 79% of TMB-high tumors with >20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.

Immune checkpoint inhibitors have changed the treatment paradigm for patients with cancer. Though a majority of patients tolerate treatment, some develop hematologic toxicities, including eosinophilia. Eosinophilia has been associated with better responses in some patients with melanoma, but this has not been investigated in non-small-cell lung cancer. We present a case of a woman with metastatic lung adenocarcinoma who developed asymptomatic hypereosinophilia after initiation of nivolumab. Her eosinophil count temporarily decreased after transiently stopping the medication, but increased again after re-initiation. She had a favorable tumor response to therapy. This exemplifies the potential role of eosinophilia as a peripheral, readily available biomarker of favorable response to immunotherapy in patients with lung cancer. Awareness of this manifestation is important.

Liquid biopsies (circulating tumor DNA—ctDNA testing) are increasingly being utilized in clinical trials as well as practice for the detection of cancer, monitoring of tumor genomic abnormalities, response to treatment and early detection of relapse/recurrence. Here, we present a challenging case where liquid biopsy was used to confirm an early recurrence of pancreatic cancer where acquisition of tissue was not safe or feasible on more than one occasion.

2033 Background: As systemic therapy improves; the prevalence of brain metastases is increasing. Screening brain MRIs are currently recommended for all stage ≥ II non-small cell lung cancer (NSCLC) and stage IIIB–IV melanoma patients, but only when neurologic symptoms arise in stage IV or recurrent breast cancer (BC) patients. This study assessed the presentation and institutional outcomes treating brain metastases (BM) of BC, NSCLC, and melanoma origin. Methods: Patients with BM treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Characteristics of initial BM diagnoses were retrieved from clinical chart review. Kruskal-Wallis and Pearson’s chi-square tests were used to test differences between groups. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan–Meier method. Results: A total of 959 patients were identified (BC 18%, NSCLC 51%, melanoma 31%). BC patients were younger at initial presentation (BC median age: 57, NSCLC 65, melanoma 62, p< 0.0001). At BM diagnosis, BC patients were more likely to have concurrent systemic metastasis (BC 77%, NSCLC 42%, melanoma 69%, p< 0.0001), at least 5 BM (BC 27%, NSCLC 14%, melanoma 13%, p= 0.0004), and leptomeningeal disease (BC 23%, NSCLC 6%, melanoma 6%, p< 0.0001). Patients with BC were significantly more likely to receive whole brain radiation therapy (WBRT) (BC 58%, NSCLC 37%, melanoma 22%, p< 0.0001) and less likely to receive stereotactic radiation (BC 26%, NSCLC 48%, melanoma 58%, p< 0.0001) following initial BM diagnosis. There were no significant differences in surgical resection between cancer types (BC 24%, NSCLC 24%, melanoma 29%, p =0.166). Median OS was shorter for BC (BC 9.9 months, NSCLC 10.3 months, melanoma 13.7 months, p= 0.0006) following BM diagnosis. Conclusions: Our institutional analysis found BC patients were more likely to be younger, present with more advanced brain disease, require WBRT, and have poorer OS than NSCLC and melanoma patients following initial brain metastasis diagnosis. This may be due in part to a lack of brain MRI screening recommendations in BC. Further investigation is needed to determine which BC patients are at sufficient risk to warrant brain MRI screening.

578 Background: TVEC is a modified oncolytic herpes simplex 1 (HSV1) virus currently FDA approved for the treatment of unresectable cutaneous and nodal melanoma. TVEC is designed to preferentially lyse tumor cells over normal tissue to release tumor associated antigens, produces GM-CSF to activate dendritic cells, and stimulates T cells to infiltrate the tumor (TILs). TILs in breast cancer are associated with better response to neoadjuvant chemotherapy (NAC), so we hypothesized that intratumoral TVEC may enhance response to NAC. We report results of a phase 2 trial combining NAC with TVEC in stage 2-3 TNBC. Methods: Stage II-III TNBC pts (N = 37) were to be enrolled into a single arm, optimal Simon 2 stage phase 2 trial with TVEC (10^6 PFU 1st dose then 10^8 PFU x 4 doses) weeks 1,4,6,8,10 + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone given preoperatively. Primary endpoint was residual cancer burden 0 rate (RCB0). Trial meets primary endpoint with ≥15 RCB0 responses out of 37 evaluable pts, assuming p1 = 45% vs. p0 = 30% with one sided type I error rate at 0.10 and power at 70%. Results: Forty pts were enrolled at Moffitt (5/2018 – 4/2020) and evaluable for safety with 3 pts non-evaluable for efficacy due to incomplete treatment. Study demographics: median age 49 (27-66), 67.5% White, 10% Black, 15% Hispanic, clinical stage II 83% and III 17%, node + 42%. The RCB0 rate = 16/37 (43%, 95% CI 27-61%) and additional 9 pts with RCB-1 (RCB0/1 rate 68%, 95% CI 50-82%). Toxicities did not differ significantly from expected NAC toxicities except for increased brief G1-2 fevers, chills, injection site pains. Four pts had G2-3 thromboembolic events (10%) slightly greater than expected 6% rate on NAC. Conclusions: Addition of TVEC to NAC increased RCB0 rates with manageable toxicities and warrants additional investigation in TNBC. Immune correlates and updated survival data will be presented at the meeting. Clinical trial information: NCT02779855.

Background: HR+ breast cancer has a long dormancy and steady rate of recurrence over decades from initial diagnosis. It is a misconception to think that HR+ disease has good prognosis since long term PFS and OS are only a few percent better for HR+ disease compared with HR- disease over a follow up of 20 years. Neoadjuvant endocrine therapy has been shown to be equivalent to chemotherapy but less toxicity. Aromatase inhibitors have also been shown to have immunomodulatory activity. In order to improve short term and long term outcomes, we started an investigator-initiated study using anastrozole plus the anti-PD-L1 antibody durvalumab in the neoadjuvant treatment of HR+/HER2- breast cancer. Methods: This is an open label, phase II with safety run-in trial conducted at Moffitt Cancer Center. The primary objective is modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0. Secondary objectives are clinical response rate, pathologic response rate, recurrence free survival. Correlative objectives include phenotypic changes in immune cells and cytokine patterns pre-, during- and post-treatment. Inclusion criteria include postmenopausal females, ECOG 0-1, HR+ with Allred score of 6 to 8, HER2-, cT2-cT4, any N, M0, appropriate lab values, agreeing to research biopsies. Exclusion criteria include multicentric disease, bilateral disease, autoimmunity or inflammatory disease, use of immunosuppressant, known HIV, Hep B/C infection, history of TB, h/o interstitial lung disease or pneumonitis, clinically significant cardiovascular disease, mean QTcF > 470 ms. Patients will receive anastrozole 1 mg PO daily for 6 months concurrently with durvalumab 1500 mg IV every 4 weeks for 6 cycles, followed by definitive surgery. Results: This is a trial in progress. However, limited preliminary results will be presented. Conclusion: The combination of anastrozole and durvalumab may lead to improved mPEPI score in the short term and improved RFS in the long term. Citation Format: Hung T Khong, Dawn N Goodridge, Nazanin Khakpour, M. Catherine Lee, Christine Laronga, Avan J Armaghani, Aixa E Soyano-Muller, Hyo Han, Hatem Soliman, Ricardo Costa, Loretta Loftus, Susan J Hoover, John V Kiluk, Zena Jameel, Brian J Czerniecki. A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-15-01.

Background: Metastatic breast cancer is a common and devastating diagnosis. New strategies for treatment are needed to help improve outcomes. Eribulin is an anti-microtubule agent approved in 2010 for advanced breast cancer. Combination with other chemotherapeutic agents provides an alternative treatment option for these patients. Purpose: This study evaluates the safety, tolerability and activity of eribulin and weekly carboplatin in a dose-escalation schema in patients with metastatic breast cancer. Methods: Patients were treated with eribulin and carboplatin AUC 2 administered on the first and eighth days of a 21-day cycle. Three doses of eribulin (0.9, 1.1 and 1.4 mg/m2) were examined. An additional 10 patients were enrolled into an expansion cohort at the recommended Phase 2 dose. Results: A total of 19 patients were treated, including 10 patients in the dose expansion cohort. There was no dose limiting toxicity related to the study therapy in the dose escalation cohorts. Grade 3 toxicities included neutropenia (21%), anemia (10%), fatigue (10%), peripheral sensory neuropathy (10%), infusion related reactions (5%), pericardial effusion (5%), diarrhea (5%) and pleural effusion (5%). Twenty-six percent of patients had grade 4 neutropenia, but there were no events of sepsis or febrile neutropenia. The maximum tolerated dose (MTD) of eribulin in combination with carboplatin AUC 2 was determined to be 1.4 mg/m2. Four patients experienced clinical benefit, 2 patients with stable disease greater than 6 months and 2 patients with partial response, demonstrating a clinical benefit rate of 21%. Conclusion: Eribulin and weekly carboplatin appeared to be safe and well tolerated with demonstrated clinical benefit. The recommended Phase 2 dose level was 1.4 mg/m2 of eribulin. Further studies can be pursued for this combination regimen to establish its efficacy.

Background: IFN-γ, a cytokine that plays diverse roles in innate and adaptive immunity, has been shown to be essential in anti-tumor immune response. In vitro and in vivo studies have shown the synergistic effect of IFN-γ in combination with HER2-targeting monoclonal antibodies with or without taxane chemotherapy. We previously conducted a phase I trial of IFN-γ in combination with paclitaxel, trastuzumab and pertuzumab (IPTP) in metastatic HER2-positive breast cancer (HER2+BC) based on which we initiated a phase II neoadjuvant study with this combination. Methods: Early stage HER2+BC patients were eligible. Treatment included 12 weeks of weekly paclitaxel 80 mg/m2 IV, trastuzumab IV every 3 weeks x 4 (8 mg/kg loading dose, then 6 mg/m2) and pertuzumab IV every 3 weeks x 4 (840 mg loading dose, then 420 mg) in combination with IFN-γ 50 mcg/m2 subcutaneous injection three times weekly starting on day 1. The primary objective was to evaluate the pathologic complete response rate (pCR) in breast and nodes. This study had a planned interim analysis after 23 patients were evaluable for pCR based on a Simon's two stage design with 90% power and a type I error rate of 0.1. The final proportion of hormone receptor (HR) status among accrued patients will be used for comparison to historical control because pCR is expected to be lower for HR+HER2+BC compared to HR-HER2+BC subtype (25% vs 50% respectively). Here we are reporting the planned interim analysis results. Results: Twenty three patients were enrolled between 1/2018 and 7/2019. Most patients had clinical stage II/III (86%) and 43% were clinically and pathologically node positive. Nineteen out of 23 (82%) had HR+ and 3 had invasive lobular carcinoma. The pCR for all patients was 52% (12/23). The pCR for HR+HER2+ and HR-HER2+ BC subgroup was 57% (11/19) and 25% (1/4) respectively. Further evaluation using RCB (residual cancer burden) showed 12 pts RCB-0, 5 RCB-I, 5 RCB-II, and 1 RCB-III. Two SAE included pneumonitis/heart failure and hematochezia. The most frequently observed grade 1 and 2 AEs were fatigue (69%), diarrhea (59%), rash (41%) and nausea (41%). Grade 3 toxicities (4% or higher) included diarrhea (n=3) and no grade 4 AE was noted. Conclusion: The addition of IFN-γ to neoadjuvant chemotherapy using paclitaxel, trastuzumab and pertuzumab was well tolerated with manageable toxicities. This study evaluated de-escalated treatments only 12 weeks duration and the anthracycline-free regimen which was highly effective with pCR of 52%. The pCR for HR+HER2+BC subtype was 57% which compares favorably to the expected pCR of 25% with neoadjuvant chemotherapy alone in HR+HER2+ patients. This regimen met the criteria to proceed to the second stage of the phase II trial and appears promising especially in HR+HER2+BC. Updated results will be presented at the meeting including correlative studies. Citation Format: Hyo S. Han, Dawn Goodridge, Avan Armaghani, Ricardo Costa, Aixa Soyano Muller, Loretta Loftus, Hatem Soliman, Brooke Fridley, Laila Khazai, Aiana Cerezo, Jesse Hevia, Marilin Rosa, Hung Khong, Brian Czerniecki. A phase II neoadjuvant trial of Interferon-gamma plus weekly paclitaxel, trastuzumab and pertuzumab in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT185.

Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint risk to evaluate novel agents as neoadjuvant therapy for breast cancer. The primary endpoint is pathologic complete response (pCR, ypT0/is ypN0)). DNA repair deficiency in cancer cells can lead to immunogenic neoantigens, activation of the STING pathway, and PARP inhibition can also upregulate PD-L1 expression. Based on these rationales we tested the combination of durvalumab (anti-PDL1), olaparib (PARP inhibitor) and paclitaxel in I-SPY2. Methods: Women with tumors ≥ 2.5 cm were eligible for screening. Only HER2 negative (HER2-) patients were eligible for this treatment, hormone receptor positive (HR+) patients had to have MammaPrint high molecular profile. Treatment included durvalumab 1500 mg every 4 weeks x 3, olaparib 100 mg twice daily through weeks 1-11 concurrent with paclitaxel 80 mg/m2 weekly x 12 (DOP) followed by doxorubicin/cyclophosphamide (AC) x 4. The control arm was weekly paclitaxel x 12 followed by AC x 4. All patients undergo serial MRI imaging and imaging response at 3 & 12 weeks combined with accumulating pCR data are used to estimate, and continuously update, predicted pCR rate for the trial arm. Regimens “graduation with success” when the Bayesian predictive probability of success in a 300-patient phase 3 neoadjuvant trial in the appropriate biomarker groups reaches > 85%. Results: A total of 73 patients received DOP treatment including 21 HR- tumors (i.e. triple-negative breast cancer, TNBC) and 52 HR+ tumors between May 2018 - June 2019. The control group included 299 patients with HER2- tumors. The DOP arm graduated in June 2019, 13 months after enrollment had started, for all HER2- negative and the HR+/HER2- cohorts with > 0.85% predictive probabilities of success. 72 patient completed surgery and evaluable for pCR, the final predicted probabilities of success in a future phase III trial to demonstrate higher pCR rate with DOP compared to control are 81% for all HER2- cancers (estimated pCR rate 37%), 80% for TNBC (estimated pCR rate 47%) and 74.5% for HR+/HER2- patients (estimated pCR rate 28%). Association between pCR and germline BRCA status and immune gene expression including PDL1 will be presented at the meeting. No unexpected toxicities were seen, but 10 patients (14%) had possibly immune or olaparib related grade 2/3 AEs (3 pneumonitis, 2 adrenal insufficiency, 1 colitis, 1 pancreatitis, 2 elevated LFT, 1 skin toxicity, 2 hypothyroidism, 1 hyperthyroidism, 1 esophagitis). Conclusion: I-SPY2 demonstrated a significant improvement in pCR with durvalumab and olaparib included with paclitaxel compared to chemotherapy alone in women with stage II/III high-risk, HER2-negative breast cancer, improvement was seen in both the HR+ and TNBC subsets. Citation Format: Lajos Pusztai, Hyo S. Han, Christina Yau, Denise Wolf, Anne M. Wallace, Rebecca Shatsky, Teresa Helsten, Judy C. Boughey, Tufia Haddad, Erica Stringer-Reasor, Carla Falkson, A. Jo Chien, Rita Mukhtar, Anthony Elias, Borges Virginia, Rita Nanda, Douglas Yee, Kevin Kalinsky, Kathy S. Albain, Aixa Soyano Muller, Kathleen Kemmer, Amy S. Clark, Claudine Isaacs, Alexandra Thomas, Nola Hylton, W. Fraser Symmans, Jane Perlmutter, Michelle Melisko, Hope S. Rugo, Richard Schwab, Amy Wilson, Amy Wilson, Ruby Singhrao, Smita Asare, Laura J. van't Veer, Angela M. DeMichele, Ashish Sanil, Donald A. Berry, Laura J. Esserman, Trial Consortium I-SPY 2. Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT011.

Background: During the natural progression of early breast cancer, it has been demonstrated that the protective host immune response against HER2 is lost early on. Using a type 1 dendritic cell (DC1) vaccine loaded with HER2 peptides has been shown to be effective in restoring anti HER2 immune responsiveness and can lead to regression of very early non-invasive breast cancers. Prior investigations conducted by our group has suggested DC vaccines may sensitize cancers to subsequent systemic chemotherapy, and the Geparnuevo trial also suggested a prechemotherapy dosing with checkpoint therapy may improve pathologic complete response (pCR) rates in TNBC. We launched a pilot study to demonstrate safety, feasibility, and preliminary efficacy of administering the DC1 HER2 vaccine for 3 weeks prior to the initiation of neoadjuvant systemic therapy for stage II-III ER-HER2+ breast cancer. Methods: This single site study is a pilot design with a safety run in phase (n = 12) followed by an expansion cohort of 18 patients. Patients with stage II-III ER-HER2+ breast cancer who are eligible to receive neoadjuvant HER2 based chemotherapy (TCHP) can enroll. The safety run in evaluates two schedules of DC1 vaccination (ARM A = once weekly x 3 weeks and ARM B = twice weekly x 3 weeks) and will enroll six patients in each arm. After the first 3 weeks of DC1 neoadjuvant chemotherapy will be administered using standard docetaxel, carboplatin, trastuzumab, and pertuzumab given intravenously once every 3 weeks for 6 cycles. Booster vaccines will be given at weeks 25, 56, 80, and 104 and immune monitoring will be performed at these timepoints. The safety run in will evaluate safety using CTCAE 4.03 criteria along with the immunogenicity of each arm measured by ELISPOT. The arm with the best immune response at 3 weeks will be selected to proceed forward during the expansion cohort using an endpoint of pCR. Secondary endpoints will be recurrence free survival rate at 3 years and immune response. The pilot design is hypothesis generating but is likely able to detect a significant difference in pCR if the true rate is 75% assuming a historical rate of 55%. Accrual to the safety run in phase is complete and the expansion phase is underway using the twice weekly vaccination schedule. Citation Format: Hatem Soliman, Deanna Hogue, Hyo Han, Hung Khong, Ricardo Costa, Avan Armaghani, Axia Soyano Muller, Nazanin Khakpour, Marie C Lee, John Kiluk, Brian Czerniecki. A pilot study utilizing a HER2 directed dendritic cell vaccine during neoadjuvant therapy of HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-06.

Background Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. Patient and methods We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. Results We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24–3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17–2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54–4.05; P

Tomo-e Gozen (Tomo-e) is a wide field optical camera for the Kiso 1.05 m f/3.1 Schmidt telescope operated by the University of Tokyo. Tomo-e is equipped with 84 chips of front-illuminated CMOS image sensors with a microlens array. The field of view is about 20 square degrees and maximum frame rate is 2 fps. The CMOS sensor has 2160x1200 pixels and a size of pixel is 19 microns, which is larger than those of other CMOS sensors. We have evaluated performances of the CMOS sensors installed in Tomo-e. The readout noise is 2.0 e- in 2 fps operations when an internal amplifier gain is set to 16. The dark current is 0.5 e-/sec/pix at room temperature, 290K, which is lower than a typical sky background flux in Tomo-e observations, 50 e-/sec/pix. The efficiency of the camera system peaks at approximately 0.7 in 500 nm.

The Tomo-e Gozen is a wide-field high-speed camera for the Kiso 1.0-m Schmidt telescope, with a field-of-view of 20.7-deg2 covered by 84 chips of 2k x 1k CMOS image sensors with 19-μm pixels. It is capable to take consecutive images at 2-fps in full-frame read with an absolute time accuracy of 0.2 millisecond. The sensors are operated without mechanical coolers owing to a low dark current at room temperature. A low read noise of 2-e- achieves higher sensitivity than that with a CCD sensor in short exposures. Big data of 30-TBytes per night produced in the 2-fps observations is processed in real-time to quickly detect transient events and issue alerts for follow-ups.

The Mid-Infrared Multi-field Imager for gaZing at the UnKnown Universe (MIMIZUKU) is a mid-infrared camera and spectrograph developed as a first-generation instrument on the University of Tokyo Atacama Observatory (TAO) 6.5-m telescope. MIMIZUKU covers a wide wavelength range from 2 to 38 μm and has a unique optical device called Field Stacker which realizes accurate calibration of variable atmospheric transmittance with a few percent accuracy. By utilizing these capabilities, MIMIZUKU realizes mid-infrared long-term monitoring, which has not been challenged well. MIMIZUKU has three optical channels, called NIR, MIR-S, and MIR-L, to realize the wide wavelength coverage. The MIR-S channel, which covers 6.8–26 μm, has been completed by now. We are planning to perform engineering observations with this channel at the Subaru telescope before the completion of the TAO 6.5-m telescope. In this paper, we report the results of the laboratory tests to evaluate the optical and detector performances of the MIR-S channel. As a result, we confirmed a pixel scale of 0.12 arcsec/pix and a vignetting- free field of view of 2./0 1./8. The instrument throughputs for imaging modes are measured to be 20–30%. Those for N - and Q -band spectroscopy modes are 17 and 5%, respectively. As for the detector performance, we derived the quantum efficiency to be 40–50% in the mid-infrared wavelength region and measured the readout noise to be 3000–6000 electrons, which are larger than the spec value. It was found that this large readout noise degrades the sensitivity of MIMIZUKU by a factor of two.

Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body’s immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.

Maternal and child health (MCH) handbooks are comprehensive home-based booklets designed to integrate MCH records. Although empirical evidence suggests the handbooks are more effective than current card-type records, this has not been scientifically demonstrated. The objectives of this study were to evaluate the impact of the MCH handbook on maternal knowledge and behaviour as measured by antenatal care (ANC) attendance, delivery with skilled birth attendants (SBAs) and delivery at a health facility. The Cambodian version of the MCH handbook was developed and introduced in two health centres, and two other health centres served as controls. Pre-intervention and post-intervention surveys were conducted with 320 women from the intervention areas and 320 women from the control areas who had given birth within 1 year before the survey. We evaluated the impact of the handbook by using difference-in-differences (DID) analysis and calculated adjusted odds ratios for pre-post changes in key indicators by using logistic regression. In addition, we interviewed multiparous women, health staff and health volunteers to assess the acceptance and cultural appropriateness of the handbook. Content analysis was performed with the English-translated transcriptions. The DID analyses revealed that all key indicators increased in the intervention group against counterfactual assumptions. The intervention also increased maternal knowledge of all topics addressed except for the risk of severe bleeding after delivery; this may be attributable to the influence of cultural belief. Logistic regression showed that the intervention increased ANC attendance, delivery with SBAs and delivery at a health facility, even after adjusting for maternal age, education and economic conditions. The qualitative data indicated that the handbook was well received and culturally appropriate. Thus, the MCH handbook is a reasonable and superior alternative to current card-type maternal records.

Pertuzumab is a monoclonal antibody against HER-2. Diarrhea and abdominal pain are common adverse events of pertuzumab-based therapy, occurring in almost 70% of patients. The incidence of gastrointestinal toxicities intensifies when pertuzumab is given in combination with chemotherapy. Rifaximin, a non-absorbable oral antibiotic, may provide symptomatic relief in patients with refractory gastrointestinal toxicities from pertuzumab-based therapy beyond standard routine antidiarrheal medications. We present a case of HER-2 related therapy induced diarrhea and abdominal pain managed successfully with Rifaximin.

Background: Immune checkpoint inhibitors (ICPIs) have led to dramatic improvement in outcome of several cancers. Program death ligand1 (PD-L1) staining and tumor mutational burden (TMB) have emerged as independent predictive biomarkers of ICPIs in lung cancer. Here we examine the landscape of TMB and PD-L1 expression in breast cancer and present a case of patient with high TMB and PD-L1 negative breast cancer with exceptional response to ICPIs. Methods: Hybrid-capture based comprehensive genomic profiling of 395 cancer related genes using the FoundationOne assay was performed on 14,867 breast carcinomas sequenced in the course of routine clinical care. Ventana (SP-263) PD-L1 status (n=1425) and hormone receptor status was available for a subset of patients. Subgroup analyses were performed based on histological type [invasive lobular carcinoma (ILC, n=740)], molecular subtypes [ER-positive (ER+; n= 1371), HER2-amplified (HER2+; n=1522), and TNBC (n=917)], patient age (≤45, 46-60, ≥61), and local vs. metastatic disease (n=5241 and 6710). Results: Consistent with previous reports, the rates of positive PD-L1 staining are highest in TNBC (14%) and lowest in HER2+, ILC, and ER+ disease (6.0%, 5.1%, 2.3%). Interestingly, the rate of PD-L1 positivity, defined as ≥1% tumor staining, was significantly lower in metastatic disease vs. local disease (6.3% vs. 11.1%; p = 0.005). The frequency of high TMB, defined as >10 mutations/mb, was greatest in ILC and HER2+ disease (13.6% and 9.9%) and lowest in TNBC and ER+ disease (7.0% and 6.9%). Rates of high TMB were associated with increased patient age (3.7%, 9.3%, and 12.8% frequency in patients ≤45, 46-60, and ≥61) and were significantly higher in metastatic vs. local disease (11.1% vs 5.3%; p20 mut/mb), there was a significant association between TMB and PD-L1 positivity (OR = 2.6, p = 0.023). Nevertheless, even with high cutoff, 79% of the TMB high samples were PD-L1 negative. We also report on a stage IIIb (T4, N2, M0) ER+ HER2- breast cancer patient with high TMB (40muts/mb) and negative PD-L1 IHC who previously progressed on aromatase inhibitor with CDK4/6 inhibitor and chemotherapy but achieved durable complete response of > 1 year with nivolumab in combination with capecitabine. Conclusions: Predictive biomarkers for ICPIs are critical to identify a subset of breast cancer patients who may respond to immunotherapy. TMB high and PD-L1 positivity do not significantly co-occur and the majority of TMB high cases were PD-L1 negative. Nevertheless, this group of patients may still benefit with ICPIs. Further studies are needed to evaluate this subset of patients. Citation Format: Ethan Sokol, Lee Albacker, Aixa Soyano, Ricardo Parrondo, Brenda Ernst, Emmanuel Gabriel, Garrett Frampton, Jeffrey Ross, Siraj Ali, Jon Chung, Saranya Chumsri. Incidence of high tumor mutation burden (TMB) and PD-L1 positivity in breast cancers and potential response to immune checkpoint inhibitors (ICPIs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4894.

Simultaneous-color Wide-field Infrared Multi-object Spectrograph, SWIMS, is one of the first generation instruments for University of Tokyo Atacama Observatory 6.5m Telescope where almost continuous atmospheric window from 0.9 to 2.5μm appears, thanks to the high altitude and dry climate of the site. To utilize this excellent condition, SWIMS is capable of simultaneous two-color imaging with a field of view of 9’. in diameter and λ/Δλ ~1000 multi-object spectroscopy at 0.9–2.5μm in a single exposure, utilizing a dichroic mirror inserted in the collimated beam. Here, we overview the instrument, report results of its full-assembly tests in the laboratory and present the future plan.

The Tomo-e Gozen is an extremely wide-field optical camera for the Kiso 1.0-m Schmidt telescope. It is capable of taking consecutive frames with a field-of-view of 20 deg2 and a sub-second time-resolution, which are achieved by 84 chips of 2k×1k CMOS sensor. This camera adopts unconventional designs including a lightweight structure, a nonvacuumed and naturally-air cooled system, front-side-illuminated CMOS sensors with microlens arrays, a sensor alignment along a spherical focal plane of the telescope, and massive readout electronics. To develop technical components necessary for the Tomo-e Gozen and confirm a feasibility of its basic design, we have developed a prototype-model (PM) of the Tomo-e Gozen prior to the final-model (FM). The Tomo-e PM is equipped with eight chips of the CMOS sensor arranged in a line along the RA direction, covering a sky area of 2.0 deg2. The maximum frame rate is 2 fps. The total data production rate is 80 MByte sec-1 at 2 fps, corresponding to approximately 3 TByte night-1. After laboratory testing, we have successfully obtained consecutive movie data at 2 fps with the Tomo-e PM in the first commissioning run conducted in the end of 2015.

MIMIZUKU is the first-generation mid-infrared instrument for the university of Tokyo Atacama Observatory (TAO) 6.5-m telescope. MIMIZUKU provides imaging and spectroscopic monitoring capabilities in a wide wavelength range from 2 to 38 μm, including unique bands like 2.7-μm and 30-μm band. Recently, we decided to add spectroscopic functions, KL-band mode (λ= 2.1-4.0 μm; R =λ/Δλ ~ 210) and 2.7-μm band mode ( λ= 2.4-2.95 μm; R ~ 620), and continuous spectroscopic coverage from 2.1 to 26 μm is realized by this update. Their optical designing is completed, and fabrications of optical elements are ongoing. As recent progress, we also report the completion of the cryogenic system and optics. The cryogenic system has been updated by changing materials and structures of thermal links, and the temperatures of the optical bench and detector mounting stages finally achieved required temperatures. Their stability against instrument attitude is also confirmed through an inclination test. As for the optics, its gold-plated mirrors have been recovered from galvanic corrosion by refabrication and reconstruction. Enough image quality and stability are confirmed by room-temperature tests. MIMIZUKU is intended to be completed in this autumn, and commissioning at the Subaru telescope and scientific operations on the TAO telescope are planned in 2017 and around 2019, respectively. In this paper, these development activities and future prospects of MIMIZUKU are reported.

The telescope of the University of Tokyo Atacama Observatory has a primary mirror with a diameter in 6.5m. In order to fabricate the reflecting film initially on the mirror surface and to maintain its optical performance over a long period, we have a mirror-coating facility being installed at the summit of Co. Chajnantor (5,640m). The facility consists of a clean booth for stripping off the old film, a mirror coating chamber, and a cart with a lifter for handling the primary mirror. A conventional evaporation system with a metal pre-wetted filament array is adopted for achieving various optical requests. Among the many development items, the fabrication of the transportation and lifting cart has been already completed. It has efficient performance in load capacity (>60 tons) and maximum lifting height (1,750 mm). A cleaning machine having injection nozzles that can realize an efficient and safe cleaning sequence also been completed. A test of the evaporation system using dedicated filaments and filament boxes, which are customized to the TAO's requirements, has shown a uniform coating on a test mirror. An array pattern of the filaments has also been decided based on the coating tests to satisfy the optical specification of the telescope. A detailed design of the main chamber has been almost completed, it is only waiting for the production in the near future.