Citations

AbstractIntroductionHypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi‐cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B‐cell lymphoma.MethodsWe conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi‐cel.ResultsThis analysis included 81 patients. Two patients had no available SA levels preceding axi‐cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1‐year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups.ConclusionNotwithstanding the limitations related to the relatively small sample size, axi‐cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.

159 Background: Tumour tissue from metastatic castration-resistant prostate cancer (mCRPC) harbors frequent copy number variations (CNVs) in the phosphatidylinositol-3-kinase (PI3K)/Akt-signaling pathway. However, identifying CNVs in plasma cell-free DNA (cfDNA) has proven challenging. With emerging data supporting Akt inhibition in PTEN-deficient mCRPC, cfDNA assays for robustly identifying PI3K/Akt pathway aberrations including CNVs are urgently required. Methods: In this multi-institutional prospective biomarker study, we used the Predicine cfDNA assay, optimised for CNV detection, to perform targeted sequencing in 231 mCRPC patients in two independent cohorts (Australian, n = 78; US, n = 153). Kaplan-Meier survival estimates and multivariable Cox regression analysis were used to assess associations between genomic aberrations and progression-free survival (PFS) and overall survival (OS). Results: PTEN loss and PIK3CA gain were detected in 37% (85/231) and 17% (39/231) of patients, respectively. Poorer outcomes were observed in patients with PI3K/Akt pathway aberrations, including those with dual PTEN loss and PIK3CA gain (HR 2.3, 95% CI 1.2-4.4). Similarly, cumulative CNV burden in the PI3K/Akt and AR pathways (0 vs 1 vs ≥2 CNVs in Australian cohort: median OS 33.5 vs 17.2 vs 9.7 months, p< 0.001; 0 vs 1 vs ≥2 CNVs in US cohort: median OS 35.5 vs 14.3 vs 9.2 months, p< 0.001) was associated with significantly worse clinical outcomes. Notably, 21% (31/146) of PTEN-neutral patients harbored other alterations in the PI3K/Akt pathway. Conclusions: Our cfDNA assay readily detected PI3K/Akt pathway CNVs, with the prevalence of PTEN loss comparable to prior tissue sequencing studies. CNVs in the PI3K/Akt pathway were associated with deleterious clinical outcomes, especially when concurrent with AR gain. Additional PI3K/Akt pathway aberrations were found in approximately one-fifth of PTEN-neutral mCRPC. Collectively, our data demonstrate the potential utility of profiling cfDNA to facilitate and optimize patient selection for treatment with Akt inhibitors in mCRPC. [Table: see text]

Background: The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Methods: Children with an age-adjusted body mass index (BMI) percentile ≥85 ( N = 130; age 8–11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Results: Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 ( P < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen ( P < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits ( P < 0.05) from the 6- to 12-month follow-up. Conclusions: The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).

Preoperative planning is critical for success in the surgical suite. Current techniques for surgical planning are limited; clinicians often rely on prior experience and medical imaging to guide the decision-making process. Furthermore, two-dimensional (2D) presentations of anatomical structures may not accurately portray their three-dimensional (3D) complexity, often leaving physicians ill-equipped for the procedure. Although 3D postprocessed images are an improvement on traditional 2D image sets, they are often inadequate for surgical simulation. Medical 3D printing is a rapidly expanding field and could provide an innovative solution to current constraints of preoperative planning. As 3D printing becomes more prevalent in medical settings, it is important that clinicians develop an understanding of the technologies, as well as its uses. Here, we review the fundamentals of 3D printing and key aspects of its workflow. The many applications of 3D printing for preoperative planning are discussed, along with their challenges.

AbstractObjectiveIn people with low‐grade intrinsic brain tumors, an epileptic focus is often located close to the lesion. High‐frequency oscillations (HFOs) in electrocorticography (ECoG) might help to delineate this focus. We investigated the relationship between HFOs and low‐grade brain tumors and their potential value for tumor‐related epilepsy surgery.MethodsWe analyzed pre‐ and postresection intraoperative ECoG in 41 patients with refractory epilepsy and a low‐grade lesion. Electrodes were designated as overlying the tumor, adjacent resected tissue (peritumoral), or outside the resection bed using magnetic resonance imaging (MRI) and intraoperative photographs. We then used a semiautomated approach to detect HFOs as either ripples (80–250 Hz) or fast ripples (250–500 Hz).ResultsThe rate of fast ripples was higher in electrodes covering tumor and peritumoral tissue than outside the resection (p = .04). Mesiotemporal tumors showed more ripples (p = .002), but not more fast ripples (p = .07), than superficial tumors. Rates of fast ripples were higher in glioma and extraventricular neurocytoma than in ganglioglioma or dysembryoplastic neuroepithelial tumor (DNET). The rate of ripples and fast ripples in postresection ECoG was not higher in patients with residual tumor tissue on MRI than those without. The rate of ripples in postresection ECoG was higher in patients with good than bad seizure outcome (p = .03). Fast ripples outside the resection and in post‐ECoG seem related to seizure recurrence.SignificanceFast ripples in intraoperative ECoG can be used to help guide resection in tumor‐related epilepsy surgery. Preresection fast ripples occur predominantly in epileptogenic tumor and peritumoral tissue. Fast ripple rates are higher in glioma and extraventricular neurocytoma than in ganglioglioma and DNET.

Abstract Background: Overall, patients with cancer experience a greater risk of adverse outcomes following SARS-CoV-2 infection; however, little is known for those with BC. Methods: CCC19 (NCT04354701) is an international cohort study aimed at investigating the impact of COVID-19 in patients with a history of or active cancer using de-identified data on patient demographics, cancer history, clinical course and outcomes of COVID-19. The current analysis includes patients from U.S. and Canada with invasive BC and laboratory-confirmed SARS-CoV-2 entered between March 17, 2020 and July 2, 2020. Co-primary outcomes were hospitalization during COVID-19 illness and 30-day all-cause mortality. Frequencies for categorical variables and medians (range) for continuous variables were estimated. Final presentation will include bivariable and multivariable Cox proportional hazards regression analysis to identify risk factors (including BC subtypes and therapies, for which data collection is ongoing) associated with 30-day all-cause mortality and severe COVID-19 illness (composite of any hospitalization requiring supplemental oxygen, admission to an intensive care unit [ICU], use of mechanical ventilation, or death). Results: During the study period, a total of 2683 patients with cancer and COVID-19 were accrued in the CCC19 registry including 529 (20%) with invasive BC. Among patients with BC, 352 (67%) were 60 years or older; 518 (98%) were women; 275 (52%) non-Hispanic White, 116 (22%) non-Hispanic Black, 70 (13%) Hispanic, 56 (11%) in other categorizations; 178 (34%) had a smoking history; 75 (14%) ECOG performance status ≥2; 191 (36%) with &gt;2 active comorbidities; 64 (12%) with AJCC stage IV disease at BC diagnosis; and 267 (50%) were on anti-cancer treatment including systemic therapy, radiation, or surgery within 3 months of COVID-19 diagnosis. At least 323 (61%) patients with BC had 30-day follow-up after COVID-19 diagnosis, and 35 (7%) had 90-day follow-up. COVID-19 illness at initial diagnosis required outpatient care in 288 (54%), inpatient care in 193 (36%), and ICU care in 40 (8%). Overall, 247 (47%) were hospitalized and 30-day all-cause mortality was 9%. 30-day all-cause mortality rates by receipt of major BC treatment modalities (within past 3 months) were: 10% for those on cytotoxic systemic therapy vs 5% and 12% for noncytotoxic systemic therapy and local therapy, respectively. The table shows hospitalization and mortality outcomes by major demographic and BC treatment strata. The final presentation will incorporate the latest patient accrual and evaluate independent clinical risk factors associated with serious COVID-19 outcomes in patients with BC. Conclusions: This represents the largest study to date of COVID-19 outcomes in patients with invasive BC. Nearly half of the patients with BC required hospitalization during their COVID-19 disease course and we observed a 9% 30-day all-cause mortality. Submitted on behalf of the COVID-19 and Cancer Consortium (ccc19us.org) Table 1. COVID-19 related hospitalization and 30-day all-cause mortality for all patients with invasive BCNAny Hospitalization30-day all-cause MortalityN% [95% CI]N% [95% CI]Total population52924747 [42-51]499 [7-12]Age&lt;601774425 [19-32]21 [0-4]60-691155144 [35-54]87 [3-13]70-791206655 [46-64]1714 [8-22]80+1178674 [65-81]2219 [12-27]ECOG PS0-132212238 [33-43]165 [3-8]2+756181 [71-89]1621 [13-32]Active Comorbidities0741014 [7-23]00 [0-5]1-22239442 [36-49]178 [5-12]&gt;219112968 [60-74]2915 [10-21]Treatment IntentCurative1866434 [28-42]95 [2-9]Palliative743953 [41-64]1216 [9-27]Cancer StatusRemission/NED33115447 [41-52]247 [5-11]Active disease, stable or responding to treatment1194840 [31-50]76 [2-12]Active disease, progressing372773 [56-86]1130 [16-47]Treatment Modality (within 3 months)Cytotoxic chemotherapy833542 [31-54]810 [4-18]Noncytotoxic therapy1856435 [28-42]105 [3-10]Local therapy (surgery or radiation)341750 [32-68]412 [3-27] Citation Format: Ali Raza Khaki, Dimpy P Shah, Maryam B Lustberg, Melissa K Accordino, Daniel G Stover, Gayathri Nagaraj, Donna R Rivera, Edith A Perez, Sara M Tolaney, Jeffrey Peppercorn, Petros Grivas, Jeremy L Warner, Corrie A Painter, Gilberto de Lima Lopes, Jr, Solange Peters, Michael A Thompson, Toni K Choueiri, Brian I Rini, Gary H Lyman, Nicole M Kuderer, Shaveta Vinayak. Characteristics and outcomes of SARS-CoV-2 infection in patients with invasive breast cancer (BC) from the COVID-19 and cancer consortium (CCC19) cohort study [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 PS7-01.

AbstractCongenital disorders of glycosylation (CDGs) are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid biosynthesis that cause multisystem diseases. Individuals with ALG3‐CDG frequently exhibit severe neurological involvement (epilepsy, microcephaly, and hypotonia), ocular anomalies, dysmorphic features, skeletal anomalies, and feeding difficulties. We present 10 unreported individuals diagnosed with ALG3‐CDG based on molecular and biochemical testing with 11 novel variants in ALG3, bringing the total to 40 reported individuals. In addition to the typical multisystem disease seen in ALG3‐CDG, we expand the symptomatology of ALG3‐CDG to now include endocrine abnormalities, neural tube defects, mild aortic root dilatation, immunodeficiency, and renal anomalies. N‐glycan analyses of these individuals showed combined deficiencies of hybrid glycans and glycan extension beyond Man5GlcNAc2 consistent with their truncated lipid‐linked precursor oligosaccharides. This spectrum of N‐glycan changes is unique to ALG3‐CDG. These expanded features of ALG3‐CDG facilitate diagnosis and suggest that optimal management should include baseline endocrine, renal, cardiac, and immunological evaluation at the time of diagnosis and with ongoing monitoring.