Citations

Abstract Background: Partial breast irradiation (PBI) is an established option for selected patients with early stage breast cancer. The optimal technique, target volume and dose/fractionation for PBI has yet to be defined. The most studied regimen in North America (38.5 Gy in 10 fractions twice daily) has been associated with cosmetic deterioration. We hypothesized that condensing treatment and reducing the total administered dose could improve the therapeutic ratio in luminal breast cancer and DCIS based on emerging evidence that breast cancer is more sensitive than surrounding normal tissues to high dose fractions. Herein, we report cosmetic, tolerability, disease control, and patient reported outcomes of a novel ultra-accelerated PBI regimen. Methods: We conducted a single arm, three cohort trial of photon, proton, and brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically equivalent effect as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Intracavitary brachytherapy target volume was lumpectomy cavity plus 1 cm and prescribed 21 Gy in 3 fractions. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin, prescribed 21.9 Gy (RBE) in 3 fractions, and delivered with image guidance. The primary outcome was the percentage difference in patients with adverse cosmesis (defined as fair or poor cosmesis) at 3 years compared to baseline pre-PBI, as assessed by trained nurses using the 4-point Harvard breast cosmesis scale. Patients also completed quality of life surveys and self-reported cosmesis using the 4-point scale. Locoregional and distant recurrence-free survival was determined using the Kaplan-Meier method. Adverse events were assessed using CTCAE, v 4.0. Results: Between 2015 and 2017, 163 patients were treated: photons in 58, protons in 48, and brachytherapy in 57. Median patient age was 66 years. 129 (79%) patients had invasive breast cancer (all ER+) and 34 (21%) had DCIS (83% ER+). Median tumor size was 1.1 cm. Grade was 2-3 in 102 (63%). The median mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons <0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. Median follow-up was 4.1 years (IQR 3.9-5.0). The proportion of patients with adverse cosmesis (by RN assessment) was 14.3% at baseline and 3.8% at 3 years, with four patients (1 photon, 1 proton, 2 brachytherapy) experiencing cosmetic deterioration at 3 years from baseline. The proportion with adverse cosmesis by self-report at 3 years was 2.4%, with three patients (1 photon, 1 proton, 1 brachytherapy) reporting cosmetic deterioration. Four patients developed locoregional recurrence (1 photons, 2 protons, 1 brachytherapy); three were local only and one was local and distant. 4-year locoregional recurrence and distant metastasis-free survival were 97.9% and 97.4%, respectively. There were 2 treatment related ≥ grade 2 late events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life, as assessed by the patient reported outcomes version of the CTCAE, 10-point linear analog scales, and the breast cancer treatment outcomes scale. Conclusions: Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues and was associated with favorable cosmetic outcomes, disease control, and excellent long-term tolerability. This ‘precision-radiotherapy’ approach may optimize the therapeutic ratio over more aggressive radiotherapy options as well as radiotherapy omission, particularly in patients with long life expectancies. Citation Format: Robert Mutter, Tina Hieken, Todd DeWees, Arslan Afzal, Stephanie Kenison, Laura Vallow, Christopher Deufel, Nicholas Remmes, Kathryn Ruddy, Judy Boughey, Keith Furutani, Amy Degnim, James Jakub, Tamara Vern-Gross, Dean Shumway, William Wong, Samir Patel, Lisa McGee, Minetta Liu, Carlos Vargas, Daniel Visscher, Bradley Stish, Deanna Pafundi, Mark Waddle, Michael Golafshar, Michele Halyard, Kimberly Corbin, Sean Park. Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-03.

AbstractBackgroundAs targeted treatments for amyloid transthyretin cardiomyopathy (ATTR‐CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter‐defibrillator (ICD) utilization, and their impact on survival.MethodsThis is a retrospective cohort study of 130 patients with ATTR‐CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation.ResultsOf 130 patients, 42 had wild‐type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR‐CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty‐two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699).ConclusionsHigh rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR‐CM patients with a high rate of systolic heart failure.

Introduction Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%–40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. Methods and analysis This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. Ethics and dissemination This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. Trial registration number NCT02261415 .

Summary: Virtual surgical planning and three-dimensional printing have been invaluable tools in craniomaxillofacial surgery. From planning head and neck reconstruction to orthognathic surgery and secondary reconstruction of maxillofacial trauma, virtual surgical planning and three-dimensional printing allow the surgeon to rehearse the surgical plan and use patient-specific surgical guides for carrying out the plan accurately. However, the process of virtual surgical planning and three-dimensional printing requires time and coordination between the surgeon on one hand and the biomedical engineers and designers on the other hand. Outsourcing to third-party companies contributes to inefficiencies in this process. Advances in surgical planning software and three-dimensional printing technology have enabled the integration of virtual surgical planning and three-dimensional printing at the treating hospital, the point of care. This allows for expedited use of this process in semiurgent surgical cases and acute facial trauma cases by bringing the surgeon, radiologist, biomedical engineers, and designers to the point of care. In this article, the authors present the utility of EPPOCRATIS, expedited preoperative point of care reduction of fractures to normalized anatomy and three-dimensional printing to improve surgical outcomes, in the management of acute facial trauma.

Abstract Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset of 17 newly diagnosed and 5 relapsed B-ALL cases with a distinct gene expression profile and 2 universal and unique genomic alterations resulting from aberrant recombination-activating gene activation: a focal deletion downstream of PAN3 at 13q12.2 resulting in CDX2 deregulation by the PAN3 enhancer and a focal deletion of exons 18-21 of UBTF at 17q21.31 resulting in a chimeric fusion, UBTF::ATXN7L3. A subset of cases also had rearrangement and increased expression of the PAX5 gene, which is otherwise uncommon in B-ALL. Patients were more commonly female and young adult with median age 35 (range,12-70 years). The immunophenotype was characterized by CD10 negativity and immunoglobulin M positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged (CDX2/UBTF) B-ALL is a high-risk subtype of leukemia in young adults for which novel therapeutic approaches are required.

AbstractBackgroundPatients with end‐stage heart failure frequently have significant congestive hepatopathy requiring hepatology assessment prior to heart transplantation listing. An elevated Model for End‐stage Liver Disease score with modification to exclude INR (MELD‐XI) has been associated with increased mortality following heart transplantation (HT). This study's primary aim was to examine whether Child‐Turcotte‐Pugh (CTP) classification is associated with post‐transplant mortality in patients bridged to transplant with left ventricular assist devices.Methods and ResultsWe conducted a retrospective analysis of 134 patients from our center. Age, CTP class, and MELD‐XI at HT were included in the multivariate model for the primary outcome, which demonstrated a significant association between 1‐year mortality and CTP class (CTP‐A HR: .08, CI .01–.46, P < .01; CTP‐B HR: .25, CI .05–1.2, P = .08; reference group CTP‐C), and MELD‐XI (HR: 1.15; CI: 1.03–1.28; P = .01), but no significant difference for age (HR: .97; CI: .93–1.01; P = .15). Only 13/33 patients with CTP improvement after assist device also had improvement in MELD‐XI.ConclusionsPatients with relatively low MELD‐XI scores with discordantly high CTP classification may be a distinct subset for whom MELD‐XI underestimates the risk of mortality after heart transplantation compared to CTP.

Abstract Background Pancreatic neuroendocrine tumors (pNETs) are rare cancers with outcomes determined by multiple factors including grade, stage, and clinical presentation. In this study, we aimed to determine the prognosis of patients with pNETs using a large population-based database. Materials and Methods In this population-based study, we identified patients with pNETs from the SEER 18 registry (2000-2016) using a combination of ICD-O-3 and histology codes. We calculated age-adjusted incidence rates using SEER*Stat 8.3.5. In addition, we analyzed overall survival (OS) using the Kaplan-Meier method, and investigated prognostic factors using a multivariable Cox proportional hazards model. Results A total of 8944 pNETs patients were identified. Annual incidence rates increased from 0.27 to 1.00 per 100 000. This was largely explained by an increase in number of patients diagnosed with localized disease in more recent years (2012-2016). Median OS was 68 months (95% CI [64, 73]) and 5-year OS rates in localized, regional, and metastatic disease were 83%, 67%, and 28%, respectively. There was a significant improvement in OS for patients diagnosed between 2009 and 2016 (median OS 85 months) compared with those diagnosed between 2000 and 2008 (median OS 46 months) (HR 0.66; 95% CI [0.62, 0.70]). This improvement in OS was consistent across all stages. Conclusions and Relevance This study shows a steady increase pNETs incidence with notable stage migration to earlier stages in recent years. This increase in incidence is accompanied by a significant improvement in survival across different disease stages.