In this multi-institutional study, pts receiving BRT prior to CAR T therapy for BCL frequently had bulky disease yet experienced favorable PFS and OS. There were no serious toxicities attributable to BRT, and the rates of CRS and ICANS are comparable to those after CAR T alone. Comprehensive BRT associated with superior PFS.

Purpose/Objective(s) CD19-targeting chimeric antigen receptor T-cell (CART) therapy is an effective treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may limit applicability and typically require hospitalization for toxicity management. Bridging radiotherapy (RT) may be used to debulk tumor burden or maintain performance status prior to CART therapy infusion, but associations with CRS and ICANS remain unclear. We assessed associations of bridging RT with CRS and ICANS among a cohort of patients (pts) receiving commercial CART therapy. Materials/Methods 94 pts receiving tisagenlecleucel (n=66) or axicabtagene ciloleucel (n=28) for r/rABL between April 2018 and June 2020 at a single institution were retrospectively identified. 22 pts (23%) received bridging RT (B-RT group) and 72 (77%) did not (NB-RT group). CRS was graded with ASTCT and ICANS with CTCAE v5.0. Grade ≥2 CRS (CRS2) and grade ≥2 ICANS (ICANS2) were compared between B-RT and NB-RT groups using Fisher exact test. Logistic regression was used to assess associations of patient characteristics, tumor bulk metrics (metabolic tumor volume [MTV], largest lesion max diameter [LLMD], and total lesion glycolysis [TLG]), and bridging therapy with CRS2 and ICANS2. Results B-RT group had better performance status (ECOG ≥1 41% vs 68%, p=0.027) and numerically but not significantly higher MTV (median 42.6mL vs 15.2, p=0.38), LLMD (median 5.8cm vs 3.5, p=0.12), and TLG (median 298.3 mL*SUV vs 60.8, p=0.22). Median B-RT dose was 31 Gy (IQR 20-40), most commonly in 2-2.5 Gy/fraction (n=17, 77%). Grade 1, 2, and 3 CRS occurred in 27 (29%), 19 (20%), and 5 (5%) pts, respectively. Grade ≥2 CRS occurred in 4/22 pts (18%) in B-RT group vs 20/72 pts (28%) in NB-RT group (p=0.16). Univariate analysis revealed associations between the following and CRS2: MTV (odds ratio [OR] 1.02 per 10 mL, p=0.025), LLMD (OR 1.12, p=0.01), largest lesion ≥5 cm (OR 2.98, p=0.046) and TLG (OR 1.02 per 100 mL*SUV, p=0.014), but not B-RT (OR 0.58, p=0.37), bridging systemic therapy (B-ST) (OR 1.33, p=0.56) or ECOG ≥1 (OR 1.33, p=0.56). Grade 1, 2, 3, and 4 ICANS occurred in 11 (12%), 6 (6%), 5 (5%), and 2 (2%) pts, respectively. Grade ≥2 ICANS occurred in 1/22 pts (5%) in B-RT group vs 12/72 pts (17%) in NB-RT group (p=0.29). Univariate analysis revealed associations between the following and ICANS2: MTV (OR 1.02 per 10 mL, p=0.048), TLG (OR 1.02 per 100 mL*SUV, p=0.017), and a trend for ECOG ≥1 (OR 3.98, p=0.085), but not B-RT (OR 0.24, p=0.18) or B-ST (OR 1.22, p=0.75). Conclusion In this single-institution study, bridging RT was used for good performance status pts with bulky tumors and was associated with low rates of CRS and ICANS. An ongoing multi-institutional effort will help refine predictive models for these toxicity endpoints and further elucidate the role of bridging RT.

Our findings contribute to the evidence that the addition of omics in prognostic models can improve ML interpretability.

Abstract Introduction Normothermic machine perfusion (NMP) is a method of organ preservation that aims to replicate the physiological environment, achieved by perfusing the livers with a blood-based perfusate at physiological inflow pressures and temperature. NMP also permits viability assessment through evaluation of the perfusate flow rates through the portal vein and hepatic artery. In addition to this, biochemical assessment and perfusate gas analysis can be performed to provide insights into the metabolic activity of the liver. Method Discarded human liver grafts (n=6), were perfused for 24 hours. Core biopsies and perfusate samples were taken from each liver at 5 distinct time intervals over 24 hours. Core biopsies were fixed and stained with periodic acid-Schiff and analysed with Leica software to provide a quantitative estimate of the hepatocellular glycogen content. Result Hepatic glycogen concentration rose during the first hour, followed by a steady decline thereafter until the end of perfusion. Contrary to our initial hypothesis that glucose concentration within the circuit would show an inverse relationship to glycogen stores in the liver cells, we found that glucose concentration closely followed the same trend. Conclusion Change in hepatocyte glycogen content provides an important insight into the synthetic function of a liver destined for transplant. Our research suggests that glucose concentration can be used as a surrogate marker for the synthetic function of a liver on NMP and provides valuable information on the glycogen-synthesising capability of the hepatocytes. In future, this could potentially aid the decision-making process with regards to liver graft transplant viability. Take-home message Perfusate glucose concentration could provide an insight into the viability of liver transplants

In this large, multicenter experience, patients with bilateral, synchronous IOAL treated with radiotherapy alone appeared to have outcomes comparable to historical series of unilateral disease. These results would suggest bilateral IOAL can be considered a localized process and support the use of curative intent radiotherapy in this setting.

Improved normal tissue sparing compared to current dose constraint standards is achievable with contemporary RT planning techniques. These improved constraints may lead to decreased toxicity, while preserving excellent disease outcomes. Our constraints can easily be adopted as standard of care and used in conjunction with other efforts to mitigate toxicity.

RT for orbital LGNHL is associated with excellent outcomes in terms of response rates and local control. Due to the exquisite radiosensitivity of orbital LGNHL, LDRT produces similar response rates and TTOR as compared to more protracted RT courses. Present data suggests that LDRT should be considered for patients with orbital LGNHL; however, further multi-center studies with larger patient numbers are warranted to show significant associations.

Relapsed/refractory diffuse large B cell lymphoma (r/rDLBCL) confers a poor prognosis. ILROG guidelines recommend hypofractionated radiotherapy (HRT) for patients with limited life expectancies, but to our knowledge there are no supporting published data. Our study seeks to evaluate the overall response rate (ORR) and time to local recurrence (TTLR) among patients who received palliative HRT for r/rDLBCL. A retrospective review was performed for all patients who completed a course of HRT (fraction size ≥2.5Gy) for r/rDLBCL between 01/2009 and 07/2019. The following characteristics were evaluated: double hit status, cell of origin (ABC vs GCB), bulky disease (>7.5cm), HRT dose (≤20Gy vs >20Gy), and prior systemic therapy courses (≤3 vs >3). Predictors for outcomes were evaluated using Cox proportional hazards regression univariate (UVA) and multivariate (MVA) models. Overall survival (OS) and TTLR were estimated with the Kaplan Meier (KM) method. RT toxicity was graded by CTCAEv5 with hematologic toxicity calculated by the 60-day (d) nadir. 100 courses of palliative HRT were administered to 92 patients. Death was a high competing risk as 25% of patients died prior to imaging evaluation. Further analysis was limited to the 64 courses of HRT administered to 56 patients with follow up imaging. Median follow up was 5.1 months. Median HRT dose and fractions was 20Gy (range: 4 – 40) and 7 (1 – 16), respectively. Nonhematologic grade 1 (G1) and G2 RT related acute toxicities occurred in 25 (39%) and 13 (20%) patients, respectively. No G≥3 nonhematologic RT toxicities occurred. ORR was 72% with 53% achieving a CR. LC at 6 and 12 months was 76% and 54%, respectively. Median TTLR was not reached. No evaluated characteristics were significantly associated with ORR or TTLR. Patients with bulky disease trended towards a worse ORR on UVA (odds ratio 0.34, p = 0.07) and MVA (0.27, p = .07). The KM estimate of median survival was 7.1 months (95% confidence interval, 3.5 - 10.5 months). Bulky disease was significantly associated with worse OS on UVA (2.69, p = .009), but not MVA (2.28, p = .07). HRT dose >20Gy was significantly associated with better OS on UVA (0.41, p = .008) and MVA (0.45, p = .028). We report the first series to our knowledge of patients with lymphoma treated palliatively with HRT. No G≥3 nonhematologic RT toxicities were observed. Significant hematologic toxicities may be related to heavy pretreatment. r/rDLBCL is responsive to HRT in terms of ORR and LC, even with lower doses. Higher doses were associated with a survival advantage, but this may reflect selection bias. HRT is a reasonable option to palliate patients with r/rDLBCL and may be considered given the high competing risk for patient death.Abstract 3753; TableHematologic ToxicityMedian absolute differenceG3 (%)G4 (%)(-103/uL)ALC20300.22ANC13262.7Hgb23171.3Plt9970WBC17263.1 Open table in a new tab

Abstract Purpose Prone positioning has been used as a viable alternative to conventional supine position for patients receiving breast radiation therapy. However, little research has been done exploring the axial rotation of patients toward the treated breast when “sinking” into the opening of the breast board and its potentially negative effects on dosimetric outcomes, which may include increased heart and lung dose. The physician may need to move the posterior border away from the chest wall to reduce heart and lung dose. Methodology 49 consecutive female patients with left sided early stage breast cancer treated at University of California Davis Medical Center were assessed from 2015 to 2018 (age range: 42-84 years, median age: 62 years). All patients underwent prone whole breast therapy with conventional external beam radiation therapy (EBRT) at doses of 50 Gy (n = 12) or hypofractionated at 42.56 Gy (n = 37). Treatment plans and dose volumes were retrospectively analyzed for each patient. Standard tangents were designed for each patient using clinical landmarks of the midaxillary line and midsternal line, which were then compared to the delivered tangent beams. The angle created between a vertical line centered on center sternum and a line drawn from center sternum to center spinal cord served to define degree of axial rotation. Breast depth was defined by the longest horizontal length from outer rib to edge of breast on sagittal view. Patients were divided into subgroups by degree of rotation and absolute breast depth. A two tailed paired Student's t-test was used for analysis. Results Overall mean heart and lung dose were 82.2 cGy and 50.43 cGy for the entire cohort, respectively. For standard tangents, patients with degree of rotation < 5 degrees in the prone position (n = 23) had significant lung sparing as compared to patients with degree of rotation > 5 cm (n = 26) (mean lung dose: 61.8 cGy vs 129.6 cGy, p = 0.00329). This was also seen for cardiac sparing (mean heart dose: 105.9 cGy vs 183.9 cGy, p = 0.000235). Even with reduction of posterior border for treatment delivery, there remained a significant increase in mean heart and lung dose with increased rotation (p = 0.038, p = 0.046). Although not statistically significant, for patients with > 5 degrees of rotation there was a trend toward increased reduction of the posterior border of the tangent (13 mm vs. 7.5 mm, p = 0.13). A significant predictor of increased rotation was breast depth > 10 cm (p = 0.01). Patients with absolute breast depth > 10 cm (n = 23) in the prone position had significant lung sparing as compared to patients with absolute breast depth < 10 cm (n = 26) (mean lung dose: 58.6 cGy vs 40.8 cGy, p = 0.042). Conclusion To our knowledge, this is the first dosimetric comparison of prone breast therapy exploring the degree of patient roll into the prone-breast setup cavity. This study demonstrates a significant increase in mean lung and heart dose when patient rotation is greater than 5 degrees. Given this, the posterior border may have to be reduced to prevent a higher than intended dose to the heart and lung. Proper attention during simulation is important to allow for optimal dose distribution and special attention should be paid to women with smaller breast size. Citation Format: Cheng K, Hoopingarner S, Wright C, Daly M, Fragoso R, Zhao X. Dosimetric impact of patient rotation during prone breast radiotherapy [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 P3-12-25.

Clocks based on cold atoms offer unbeatable accuracy and long-term stability, but their use in portable quantum technologies is hampered by a large physical footprint. Here, we use the compact optical layout of a grating magneto-optical trap (gMOT) for a precise frequency reference. The gMOT collects 107 87Rb atoms, which are subsequently cooled to 20 µK in optical molasses. We optically probe the microwave atomic ground-state splitting using lin⊥lin polarised coherent population trapping and a Raman-Ramsey sequence. With ballistic drop distances of only 0.5 mm, the measured short-term fractional frequency stability is 2×10-11/τ.

Chimeric antigen receptor T cell (CAR-T) therapies targeting lymphoma-specific epitopes have demonstrated efficacy in relapsed/refractory non-Hodgkin lymphoma. Radiation therapy (RT) can be used as bridging therapy for symptomatic progression, and/or as lymphodepletion prior to CAR-T infusion. This tandem sequencing of RT and CAR-T has not been previously reported. Patients enrolled in a phase IIA study evaluating autologous T cells engineered to express CD19-directed CAR (NCT02030834) were divided into no RT or RT prior to infusion groups, including: induction RT (<30 days), prior RT (>30 days but <12 months), and remote RT (>12 months). CAR-T in vivo expansion, toxicity, outcomes were recorded. Median follow-up is defined as time from CAR-T infusion to event or last follow-up (f/u). Descriptive statistics were used with Kaplan-Meier analysis for progression-free (PFS) and overall survival (OS). Forty-one patients are evaluable: 18 no RT, 5 induction RT, 7 prior RT, and 11 remote RT. Patients included diffuse large B cell (61%), follicular (34%), and mantle cell lymphoma (5%). Induction RT was used to manage symptoms and incorporated into the lymphodepleting regimen in those patients. Patients in the induction RT group began RT after T cell collection, on average 12 days prior to re-infusion (range 7-19); those in the prior RT group received RT 146 days prior to T cell collection (range 99-263). Median f/u time is 674 days for all patients. One-year PFS and OS for each group are: 44 and 65% (no RT), 78 and 100% (induction RT), 0 and 86% (prior RT), and 61 and 90% (remote RT), respectively. Cytokine release syndrome, ≥ grade 3, occurred in 10 of 41 patients overall (24%), but in no patient in the induction RT group (0 of 5). CAR-T expansion and day of peak CAR-T were not affected by RT given at any interval prior to T cell collection or re-infusion. Induction RT prior to CAR-T infusion does not impact efficacy of therapy, and may be associated with a lower incidence of CRS. Given that RT can both palliate symptoms and be used in lymphodepletion regimens, this tandem approach warrants further exploration and potential consideration in future CAR-T trials.

Extremely high PVR is still a contraindication to heart transplantation. LVAD support has been shown to reduce PVR to bridge to a subsequent transplantation. However, its actual efficacy on transplant outcome remains to be clarified. The purpose of the current study is to investigate the effect of high pre-LVAD PVR on transplant outcome using the UNOS registry.

There is growing concern regarding the association between pre-transplant amiodarone use and post-transplant primary graft dysfunction (PGD). We hypothesize that amiodarone use is associated with severe PGD in a dose-dependent manner.

The 2013 ISHLT consensus statement on primary graft dysfunction (PGD) introduced use of an inotrope score as an assessment tool of graft function after orthotopic heart transplantation (OHT). The clinical relevance of this scoring system has yet to be validated. We hypothesize that inotrope score has a positive association with in-hospital mortality post-OHT.

Introduction: Though PVR 6). Demographic data were compared and odds ratios (ORs) for one-year mortality after HTx in intermediate and high PVR groups were calculated making low PVR group as baseline. Results: In a LVAD cohort, 3490 patients (2772 in low PVR, 647 in intermediate PVR, and 71 in high PVR group) were included, while in a non-LVAD cohort 5920 patients (4264 in low P...

Alhough much literature has focused on post-transplant survival in left ventricular assist device (LVAD) bridge-to-transplant (BTT) patients, there is scant research comparing overall survival from the time of initial heart replacement therapy with LVAD versus isolated heart transplant (HTx). Young patients might benefit from an LVAD-first strategy, which may allow later HTx and therefore delay the development of HTx-related complications. We sought to evaluate whether young patients treated with LVAD as BTT experienced worse mid-term survival from implantation as compared to those who underwent isolated HTx.

Welcome to Annals of Global Health,Annals of Global Health is a peer-reviewed, fully open access, online journal dedicated to publishing high quality articles dedicated to all aspects of global health. The journal's mission is to advance global health, promote research, and foster the prevention and treatment of disease worldwide. Its goals are to improve the health and well-being of all people, advance health equity, and promote wise stewardship of the earth's environment. The latest journal impact factor is 3.64.Annals of Global Health is supported by the Program for Global Public Health and the Common Good at Boston College. It was founded in 1934 by the Icahn School of Medicine at Mount Sinai as the Mount Sinai Journal of Medicine. It is a partner journal of the Consortium of Universities for Global Health. Authors of articles accepted for publication in Annals of Global Health will be asked to pay an Article Publication Charge (APC) to cover publication costs. This charge can normally be sourced from your funder or institution. We are committed to supporting authors from all countries to publish their work in Annals of Global Health regardless of national income level, and to achieve this goal, we waive the Article Publication Charge for manuscripts where all authors are from low-income or lower-middle-income countries (as defined by the World Bank). From time to time, Annals of Global Health publishes Special Collections, a series of articles organized around a common theme in global health. Recent Special Collections have included “Strengthening Women’s Leadership in Global Health”, “Decolonizing Global Health Education”, and “Capacity Building for Global Health Leadership Training”. Global health workers interested in developing a Special Collection are strongly encouraged to contact the Managing Editor in advance to discuss the project.

Implantable left ventricular assist devices (iVAD) have been widely used for patients with end-stage heart failure as a bridge to heart transplantation (HTx). There is an increasing population of patients who require bridging with a temporary ventricular assist device (tVAD), either with or without an iVAD. Outcome of these patients after HTx is unknown. Between January 2007 and April 2015 there were 430 patients cared for at this institution who underwent OHT. Patients were further grouped by the algorithm of support device prior to their HTX as no bridge (Group A, n=248), single bridge with tVAD (Group B, n=17), single bridge with iVAD (Group C, n=148) and multiple bridges with tVAD and iVAD (Group D, n=17). Primary outcome was survival after HTX. Patients in group B were more likely to be younger compared to the others (A:52±13, B:46±16, C:54±13, D:54±11, years, respectively, p=0.059) and have lower body mass index (A:25.4±5.0, B:23.6±4.6, C:27.0±4.7, D:25.6±6.3, kg/m2, respectively, p=0.008). Patients bridged with iVAD (bridge groups C and D) had lower total bilirubin at the time of HTX (A:1.2±1.0, B:1.1±0.8, C:0.9±0.8, D:0.8±0.3, p=0.078). In-hospital mortality rate after HTx was not significantly different between groups (A: 8.5%, B: 11.8%, C:11.7%, D:11.7%, p=0.660). The 1-year survival for group D was comparable to groups A and C, while 1-year survival for group B is significantly lower than any other groups (90.2%, 70.6%, 88.3% and 87.8%, respectively, p=0.018). Post HTx survival in patients requiring multiple bridges was similar to those in non-bridge or single bridge with iVAD patients.