Symptomatic Pts Research Articles

Implementing teleoncology in a safety-net hospital during the COVID-19 pandemic.

262 Background: In response to the COVID-19 pandemic, telehealth has emerged as a key strategy to ensure the safety of patients and healthcare workers and minimize disease spread. Lyndon B. Johnson Hospital (LBJ) is a safety-net hospital that mainly serves low income and uninsured patients (pts), and MD Anderson Medical Oncology faculty and fellows diagnose and treat over 800 new cancer cases per year in the LBJ Oncology Clinic. We piloted a teleoncology (TO) program to replace in-person visits for pts with clinic appointments (appts) during the COVID-19 pandemic. Methods: A multidisciplinary team was formed to implement TO in the LBJ Oncology Clinic. Fellows and APPs screened their appts in advance and used guidelines to determine pts appropriate for TO. Clinic visits were prioritized for new pts, treatment consents, and symptomatic pts; stable pts on treatment and surveillance had appts changed to TO. Pts were notified when their appts were converted, with integrated video visits preferred over telephone visits. To limit disease exposure, 3 fellows rotated in clinic for one week at a time and cared for the pooled clinic pts; the other 16 fellows and 2 APPs conducted TO and remotely staffed their pts with faculty on their assigned clinic day. We reviewed TO visits during the initial 1-month pilot period and survey results from involved personnel. Results: From 4/13/2020 – 5/8/2020, we identified 251 pts that utilized TO. Median age was 57 years (range, 20-88) and 66% were female; 63% were Hispanic and 21% were African American; 52% spoke Spanish and 46% spoke English. 57% of TO visits were conducted via telephone and 43% via video. 48% of the TO visits were for pts on active treatment, including IV therapy (35%) and oral targeted agents (13%); 15% were surveillance pts with (9%) or without (6%) restaging imaging, 8% were pts on endocrine therapy, and 16% had transitioned to the Survivorship Clinic staffed with APPs. Survey response rate was 100% (5/5) for faculty, 74% (14/19) for fellows, and 100% (2/2) for APPs. 80% of faculty, 57% of fellows, and 100% of APPs were generally satisfied (agree/strongly agree) with the patient care delivered via TO; 100% of faculty, 64% of fellows, and 100% of APPs believe patients were generally satisfied with TO. Conclusions: This study demonstrates that implementing TO in a fellows’ teaching clinic at a safety-net hospital is feasible and effective. Nearly half of the TO visits conducted during this pilot period were for pts on active cancer treatment and the majority of caregivers were satisfied with TO. Pt care via TO is ongoing and pt survey data is currently being collected.

S1330 High Discovery Rate of Previously Undiagnosed Patients With Eosinophilic Gastritis and Duodenitis Using a Systematic Endoscopic Biopsy Protocol: Screening Data Analysis From ENIGMA, a Randomized Controlled Trial

INTRODUCTION: Eosinophilic gastrointestinal (GI) disorders (EGIDs) such as eosinophilic gastritis (EG) and duodenitis (EoD) are chronic inflammatory conditions characterized by aberrant accumulation and activation of localized tissue eosinophils and mast cells. Patients (pts) with EG/EoD present with non-specific, often debilitating GI symptoms including abdominal pain and cramping, early satiety, nausea and diarrhea. Non-specific symptoms, the absence of consensus diagnostic histopathologic guidelines, and the perception of rarity contribute to a delay in diagnosis of pts with EG/EoD. While the prevalence of EG/EoD is currently estimated to be ∼50,000 in the US, this may be an underestimate. We aimed to evaluate the prevalence of EG/EoD among symptomatic patients not previously diagnosed. METHODS: We reviewed screening data from ENIGMA, a multi-center, randomized, double-blind, placebo-controlled phase 2 trial assessing the safety and efficacy of AK002, an anti-Siglec-8 monoclonal antibody, in pts with EG/EoD. Adult pts were screened with a validated, daily 8-symptom EG/EoD questionnaire to capture moderate-severely symptomatic pts. Those who met symptom inclusion criteria underwent upper endoscopy (EGD) with gastric and duodenal biopsies as per protocol (12 total: 4 biopsies each from the gastric antrum, gastric corpus, and duodenum). Symptomatic pts meeting histologic definition of EG (≥30 eos/hpf in ≥5 hpfs) and/or EoD (≥30 eos/hpf in ≥3hpfs) were eligible for randomization. RESULTS: 113 pts entered screening for ENIGMA. 51 had no prior history of EG/EoD, 26 (51%) of whom met symptom criteria and underwent screening endoscopy. Of these 26 symptomatic pts, 15 (58%) met histologic criteria for EG/EoD, 13 of whom were randomized in the study. These 13 pts, previously given functional GI diagnoses, were clinically similar in constellation and magnitude of symptoms compared to the 52 randomized pts with previously established EG/EoD. CONCLUSION: There is growing evidence that EG/EoD is underdiagnosed, and that the true US prevalence may be higher than 50,000. Among moderate-severely symptomatic pts without known history of EG/EoD who entered screening for ENIGMA, 58% met histologic criteria for EG/EoD. EGD with multiple systematic gastric and duodenal biopsies of pts with chronic non-specific GI symptoms, including those with functional GI conditions, may demonstrate a higher prevalence of EG/EoD than is currently estimated.Figure 1.: Discovery Rate of Newly Diagnosed EG/EoD Patients in ENIGMA Screening 1) Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) sites; n = 62 entered screening 2) Primarily general gastrointestinal practices and professional GI research centers; n = 51 entered screening.Figure 2.: Similar Symptom Burden in Established and Newly Diagnosed EG/EoD Patients.Table 1.: Characteristics of Established and Newly Diagnosed EG/EoD Patients

Reactivation of human herpesvirus 6 in pediatric allogeneic hematopoietic stem cell transplant recipients.

Reactivation of human herpesvirus 6 (HHV-6) occurs in 30%-50% of patients (pts) who receive allogeneic (allo) hematopoietic stem cell transplant (HCT). However, the recommendation for post-transplant HHV-6 monitoring and treatment in pediatric pts is not well established. HHV-6 incidence rates and the clinical outcomes were reported for 139 pediatric pts (≤18years) undergoing first allo-HCT at City of Hope from July 2011 to July 2017, for whom HHV-6 was monitored weekly throughout HCT hospitalization. For 57 pediatric pts, who underwent first HCT from January 2009 to July 2011, HHV-6 was tested as clinically indicated and only rates of HHV-6 viremia were collected. From July 2011 to July 2017, HHV-6 was detected in 88/139 pts (63%). The frequency of HHV-6 viremia was associated with malignant diagnoses, myeloablative conditioning, and cord blood HCT. Treatment with antiviral agents was offered to symptomatic pts with a higher viral load (VL), for whom the time to VL clearance was longer and the frequency of subsequent recurrences was higher. Pts with a lower VL cleared HHV-6 without treatment. HHV-6 viremia was associated with a higher frequency of grade II-IV acute graft-versus-host disease (GVHD) (P=.022), but did not affect overall survival (OS), disease-free survival (DFS), non-relapsed mortality (NRM), myeloid, or platelet (Plt) engraftment. HHV-6 weekly screening is not necessary for all HCT pts but may be considered for high-risk pts with malignant diagnoses undergoing cord blood HCT; otherwise, HHV-6 should be tested as clinically indicated. Only symptomatic pts (especially with a high VL>25000) could benefit from treatment. HHV-6 viremia at the time of initiation and administration of the conditioning regimen cleared promptly without the need to augment the transplant process.

448P Predictive factor of cardiotoxicity in fluoropyrimidine-treated colorectal cancer patients: Interim analysis of the prospective observational CHECKPOINT trial

Cardiotoxicity represents an unexpected and potentially life-threatening toxicity in colorectal (CRC) patients (pts) treated with fluoropyrimidines (FP). Currently, there are no predictive factors of FP-induced cardiotoxicity (FIC), moreover the correlation between FIC and known cardiovascular (CV) risk factors remains controversial. CRC FP naïve pts have been enrolled at Candiolo Cancer Institute from January 2016 to February 2020. Before the start of FP-based chemotherapy (CT), all patients were screened for CV comorbidities and potential risk factors with an optimization of the cardiological treatment if needed. During the first 3 CT cycles, pts were monitored with CV symptoms collection, serial electrocardiograms and brain natriuretic peptide (BNP) measurement, as well plasma samples were obtained. Primary objective was the incidence rate of FIC. Secondary objectives comprised the study of risk factors for FIC including BNP baseline levels and the validation of circulating microRNAs (c-miRNAs) as potential biomarkers of FIC. A total of 135 pts (60.7% men, median age 66 years) were included in the interim analysis, of whom 48.7% presented CV risk factors. During the treatment period 20 pts (15%) experienced FIC: 1 acute coronary syndrome, 1 coronary vasospasm, 1 paroxysmal supraventricular tachycardia, 1 complete left bundle branch block, 3 syncope, 4 typical chest pain, 6 sudden dyspnea and 3 sudden palpitations. A higher incidence of FIC in women (p. 0.048) was highlighted. No correlation between age (</> 75 years), cardiovascular risk (high/low), type of FP (5-fluorouracil/capecitabine) and disease status (adjuvant/metastatic) was observed. Among symptomatic pts 10 (50%) had CV comorbidities and/or CV risk factors. A decreasing trend in BNP values was observed in pts treated with capecitabine who experienced FIC, but this result did not reach statistical significance yet. Although FIC was observed in a not negligible percentage of patients, no relationship with CV comorbidities or risk factors was found. A more precise correlation of cardiac events with c-miRNAs will be available at completed recruitment (200 pts).

P301 The prognostic value of preoperative left atrial volume after surgical aortic valve replacement in patients with isolated severe aortic stenosis and preserved left ventricular ejection fraction

Abstract Background Left atrial (LA) volume is an important cardiovascular prognostic marker. However, data regarding the prognostic value of LA volume in severe AS patients (pts) after surgical aortic valve replacement (AVR) are scarce. Moreover, the predictive role of LA function in AS pts after AVR has not yet been studied. Our study aimed to assess the relationship of LA volume index (LAVi) and function with outcome, in terms of mortality, in severe AS pts who underwent surgical AVR. Methods A total of 360 consecutive pts with isolated severe AS (aortic valve area index ≤ 0.6 cm2/m2) referred to our echocardiography laboratory were prospectively screened. Two hundred and seventeen pts with preserved left ventricular (LV) ejection fraction (≥50%) and in sinus rhythm were enrolled. All patients underwent a baseline comprehensive echocardiogram, including speckle tracking analysis of both LV and LA strain. Symptomatic pts (142 pts, 65%) that were subject to AVR were followed for a median period of 4 years (IQR 3-6 years). The endpoint was all-cause mortality after AVR. The last update of the survival status was obtained in January 2019. Outcome data were available in 116 severe AS pts that underwent AVR (mean age 63 ± 10 yrs, 56% men), who formed the final study population. Results Seventeen (14%) pts died during follow-up. No significant differences were found between nonsurvivors and survivors after AVR in terms of age and cardiovascular risk factors. Nonsurvivors had higher BNP plasma values (p=.04) at baseline compared with surviving pts. Survivors and nonsurvivors alike exhibited similar preoperative AS severity and LV systolic function parameters (ejection fraction and global longitudinal strain). Moreover, there were no significant differences between the two groups regarding baseline valvuloarterial impedance, average E/e’ ratio, and LA longitudinal deformation parameters. Nonsurvivors had a tendency toward higher LV mass index (p=.08). Nonsurvivors had higher preoperative LA volume index (LAVi)(50 ± 12 vs. 44 ± 10 ml/m2, p=.003). In a multivariable Cox regression analysis adjusted for age, LAVi emerged as the only independent predictor for death in our population study (HR 1.06, 95% CI 1.01-1.11, p=.02). A cut-off value for LAVi derived from ROC curve analysis was used to construct Kaplan-Meier survival curves. A value of 43 ml/m2 for LAVi predicted all-cause mortality after AVR in severe AS pts with 71% sensitivity and 54% specificity. Conclusions In our study, preoperative LAVi predicted death in severe AS pts after surgical AVR. LAVi assessment may improve preoperative risk stratification in patients with severe AS, however further larger prospective studies are needed. Abstract P301 Figure.

Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

1244 Symptomatic Patients Suspected of Eosinophilic Gastritis and/or Enteritis Have Elevated Mucosal Mast Cell Counts Without Eosinophilia: A New Diagnostic Entity?

INTRODUCTION: Eosinophilic gastrointestinal diseases (EGIDs) are a set of inflammatory diseases subclassified according to the site(s) of abnormal accumulation of eosinophils (eos) in the gastrointestinal (GI) tract such as eosinophilic esophagitis (EoE), gastroenteritis (EGE), and colitis. These conditions often decrease quality of life due to debilitating symptoms. While the pathogenesis of EGIDs is primarily thought to be driven by eos, there is increasing evidence for the involvement of mast cells (MCs). AIM: To characterize symptomatic patients (pts) with suspected EG/EGE who did not meet histopathologic entry criteria for mucosal eosinophilia for a Phase 2 randomized, double-blind, placebo-controlled study of AK002, an anti-Siglec-8 antibody. METHODS: To undergo screening endoscopy for this study, pts were required to report an average symptom score ≥3 (0 to 10 scale) for abdominal pain, nausea, and/or diarrhea on a daily patient-reported outcome questionnaire for ≥2 weeks and have no other known cause for GI symptoms. During the screening endoscopy, biopsies were systematically obtained from the stomach and duodenum, and read by a single pathologist. Eos counts (eos/hpf; hpf area = 0.237 mm2) were assessed on H&amp;E slides. To quantify MCs, immunohistochemistry for tryptase was performed. We quantified eos and MCs in the stomach and duodenum. Histopathologic entry criteria for the randomized study was ≥30 eos/hpf in 5 hpfs in the stomach (EG) and/or ≥30 eos/hpf in 3 hpfs in the duodenum (EGE). A literature review was conducted to determine normal MC counts in the GI tract. RESULTS: Eighty-eight pts underwent screening endoscopy based upon suspected EG/EGE and active symptoms, and 72 pts met histopathologic eos criteria. All pts whose eos did not meet entry criteria (n = 16) were found to have elevated MC counts (Figure 1; reported normal range = 12-19 MCs/hpf). In these pts, the mean gastric eos count was 6 eos/hpf in 5 hpfs and mean duodenal eos count was 15 eos/hpf in 3 hpfs. In contrast, these pts exhibited a mean gastric MC count of 47 MC/hpf in 5 hpfs and a mean duodenal MC count of 49 MC/hpf in 3 hpfs. Almost all symptomatic pts screened (87/88; 99%) had elevated MC counts. CONCLUSION: Data from this large randomized EG/EGE study showed that symptomatic pts with suspected EG/EGE had increased mucosal MCs with or without mucosal eosinophilia. These data suggest that MCs may play a role in pts with suspected EG/EGE and raise the possibility of a unique clinical presentation driven by MCs.

P4657Cardiac myxomas: are we dealing with distinct clinical entities?

Abstract Background Cardiac myxomas are rare, despite being the most common primary cardiac tumours. A significant number of myxomas are discovered accidentally in asymptomatic patients (pts), as there is increased use of non-invasive cardiac imaging. Our aim was to describe the experience of a cardiac surgery centre managing cardiac myxomas during the last 28 years. Methods Single-center retrospective study of consecutive pts admitted with the diagnosis of a cardiac myxomas between 1990 and 2018. Registry data concerning clinical presentation, non-invasive imaging assessment and definitive histopathology were collected. Results From 154 pts with the diagnosis of cardiac tumours, we identified 106 (68.8%) myxomas (67% females; mean age at diagnosis 61,5±13,1 years). Myxoma diagnosis increased throughout the 3 decades (27 cases until 2000; 26 cases in the second decade; 52 cases from 2010 until present). 30% of the pts were asymptomatic at diagnosis. Obstructive symptoms (heart failure and syncope) and embolic events were the most common complaints among symptomatic pts. Transthoracic echocardiography firstly identified the tumours in 88% of the cases. Cardiac magnetic resonance and computed tomography were performed for further investigation in 7% of the cases. Presumptive pre-operative diagnosis was correct in 83.8% pts. Surgical excision was successfully achieved in all cases. 89% of the tumours were located in the left atrium with inter-atrial septum implantation (13 in right chambers; 1 valvular tumour). There were 10 multifocal tumours. At histopathology myxomas were grossly described as mucous jelly appearance (80%), solid (15%) and mixed type lesions (5%). Rare histologic findings were described in 30% of the cases (8 tumours with bone tissue; 1 with forming bone marrow; 4 with endocrine type glandular epithelium; 16 with lympho-plasmocytic infiltrates; 3 with high mitotic grade; 5 with concomitant thrombus). For a median follow up of 86 [31–214] months there were 15 deaths (2 of them with tumour related deaths). There were 3 recurrences (2 with high mitotic grade histology), mostly occurring 3 years after the first intervention. Conclusion In this case series cardiac myxomas are the most common cardiac tumours, with a significant proportion of asymptomatic lesions. Clinical heterogeneity followed polymorphic histology, with recognized differences when compared to classical descriptions of this kind of tumour.

P6581Association of neuro-psycho-behavioral troubles to catecholaminergic polymorphic ventricular tachycardia: a more severe arrhythmic phenotype?

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is defined by bidirectional or polymorphic ventricular tachycardia during adrenergic situations and is associated to a poor long-term prognosis. Clinical cases suggest an association between epilepsy and/or neuro-psycho-behavioral troubles (NPBT) to cardiac channelopathies. Methods This is a retrospective observational study based on case analysis from the INTEGRALIS database of the referral center for inherited cardiac arrythmias in Nantes. Epidemiological and clinical-biological features of the population have been studied. Patients with Presence or Absence of NPBT were compared. Results:From 8306 pts in the whole database, 533 presented with VT and 71 pts were diagnosed with CPVT and genotyped. Symptom onset occurred at a medium age of 17.1±13.5 years. Median LVEF was 65% (IQR 9,8%) and median corrected QT interval (QTc) was 399 ms (IQR 27 ms). 77.5% of pts had fainting and/or syncopes, and there were 28.2% patients with a history of cardiac arrest. Time to diagnosis was below1 year for 44.2% of symptomatic pts. Symptoms occurred during exertion for 42.3% of pts including swimming. The prevalence of NPBT was 23,9%. 74% of NPBT were convulsive seizures, 21% psycho-behavioral troubles and 5% epilepsy proved by EEG. Median age of symptom onset was younger in the group “NPBT” (12.2±4 yo vs 19.2±15.5 yo). The rate of patients with symptoms during exertion was higher in the group “NPBT” (29.4 vs 7.4% P=0.031). A mutation in the gene of Ryanodine receptor-2 was found in 64.8% of pts. Comparisons patients w/wo NPBT NPBT (N=17) Without NPBT (N=54) Familial history of Sudden death 7/17 (41.2%) 24/54 (44.4%) NS Familial history of CPVT 5/17 (29.4%) 29/54 (53.7%) NS Medium age of symptom onset (yo) 12.1±4 19.2±15.5 P=0.021 Time to diagnosis &lt;1 year 4/17 (23.5%) 16/54 (27.8%) NS Malaises and/or syncopes 17/17 (100%) 38/54 (70.4%) P=0.035 Cardiac arrest 9/17 (52.9%) 11/54 (20.4%) P=0.025 ICD Implantation 6/17 (35.3%) 12/54 (22.2%) NS Supraventricular arrhythmias 3/17 (17.7%) 6/54 (11.1%) NS Antiepileptic treatment 5/17 (29.4%) 2/54 (3.7%) P=0.009 Conclusion NPBT appears to be associated to a younger age of symptom onset and a higher rate of serious cardiac events particularly during swimming. This study will serve as preliminary data for further clinical and experimental protocols.

P1780Usefulness of multimodality imaging approach in the diagnosis of mechanical prosthetic valve dysfunction

Abstract Background Although the long-term outcome of mechanical mitral and aortic prosthetic valve (M-PV, Ao-PV), PV dysfunction (PVD) remains a very serious complication associated with high morbidity and mortality. Thrombosis/pannus and paravalvular leak are the 2 main mechanisms of PVD. The diagnosis of PVD, based on clinical presentation may be challenging, but it is essential for referring the patient to the optimal treatment (clinical follow-up, thrombolysis, surgery). An integrated multimodality imaging approach, comprising several parameters by transthoracic echocardiography (TTE) and fluoroscopy (F), is mandatory to pursue the correct therapeutic pathway. Purpose This study aims to evaluate the incremental diagnostic value of combined TTE+F over each imaging modality alone in symptomatic pts with Ao-PV or M-PV and high suspicion of PVD. Methods 387 consecutive pts (63±11y, 213 Ao-PV, 173 M-PV) suspected for PVD, symptomatic for dyspnea, embolic events, fever or haemolysis were enrolled. All patients were imaged by TTE and F within 2 days after the admission to the hospital. TTE was defined positive for PVD in presence of intra/para-prosthetic regurgitation or high transprosthetic gradient (&gt;20mmHg in Ao-PV, &gt;8mmHg in M-PV) together with altered Doppler parameters (for Ao-PV: DVI &lt;0.25, AT&gt;95ms; for M-PV: Peak Mitral Velocity&gt;2m/sec, VTIPrMV/VTILVO&gt;2.5, PHT&gt;130ms). F was defined positive for PVD when leaflet/s restriction occurs. PVD was confirmed by transoesophageal echocardiography (TOE) or positive response of thrombolysis (T), or surgical inspection (S). Results PVD was found in 46% (99/213) of Ao-PV and in 53% (91/173) of M-PV at TOE/T/S. Sensitivity (SE), specificity (SP), negative predictive value (NPV), positive predictive value (PPV) and diagnostic accuracy (ACC) for TTE, F and combined TTE+F are reported in Table. The integration of TTE+F data significantly improved ACC both for Ao-PV and M-PV. At ROC analysis, the combined model of TTE+F showed the highest AUC for the detection of PVD compared with TTE and F alone (Figure). Table 1. Comparison of diagnostic accuracy between TTE, F, and TTE+F TTE-Ao-PV (n=211) F-Ao_PV (n=204) TTE+F-Ao-PV (n=202) TTE-M-PV (n=172) F-M-PV (n=158) TTE+F-M-PV (n=157) SE / SP / NPV / PPV / ACC (%) 86 / 89 / 88 / 88 / 88 59 / 99 / 72 / 98 / 79 94 / 88 / 94 / 88 / 91 74 / 90 / 75 / 89 / 81 49 / 96 / 60 / 93 / 70 81 / 86 / 78 / 88 / 83 Figure 1. ROC curves Conclusions In patients with clinical suspicion of PVD, TTE and F are both valid tools to evaluate the PV performance. However, the combined model of TTE+F had a significant incremental value over TTE or F alone to diagnose the presence of PVD. This multimodality imaging approach allows to overcome several weaknesses of the TTE or F alone and consequently provides a prompt recognition of PVD even though TOE remains the gold standard to diagnose paravalvular Leak and non-obstructive thrombosis.

P888Left ventricular diastolic function and left atrial longitudinal function during exercise correlate with exercise capacity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical course of hypertrophic cardiomyopathy (HCM) is heterogeneous and the development of heart failure (HF) is difficult to predict. Exercise echocardiography can provide information about mechanisms involved in the occurrence of HF symptoms: development of intraventricular obstruction, increase in mitral regurgitation (MR) severity, impaired left ventricular (LV) and left atrial (LA) function. Purpose To analyse the changes in LV and LA function during exercise and to identify the main correlates of exercise capacity in patients (pts) with HCM, in sinus rhythm and with normal LV ejection fraction. Methods We have prospectively enrolled 32 pts (48±17 years, 15 men) with HCM and no obstruction at rest. A symptom limited exercise echocardiogram was performed in all pts using a table ergometer. Maximum LV wall thickness (LVWT), indexed left atrial volume (LAVi), septal E', E/septal E' ratio, were measured at rest (r) and during exercise (e). Global longitudinal LV strain (GLS) and LA strain (LAɛ) were assessed by speckle tracking echocardiography at rest and during exercise. The peak LV outflow tract gradient, systolic pulmonary artery pressure (PAP), and MR degree were recorded at rest and during exercise. Exercise-related symptoms, peak exercise heart rate (HR) and exercise capacity calculated in metabolic equivalents (METs) were also recorded. Results The mean value of achieved METs was 5.9±1.4, the peak HR was 124±25 bpm, representing 72±12% of maximal HR, during a mean of 8.5±2.5 minutes of exercise. Thirteen pts developed LV gradients &gt;30 mmHg. Fifteen pts were asymptomatic, while 17 pts reported dyspnea during exercise. There were no significant differences between pts with and without symptoms regarding: age, rE', rE/E', rGLS, rLAɛ, rMR, rPAP, LAVi, eE/e', eGLS, eMR, ePAP (p&gt;0.05 for all). Symptomatic pts had lower values for eE' (p=0.01), eLAɛ (p=0.03) and tended to have higher values for LVWT (p=0.06) and a higher prevalence of eLV outflow tract obstruction (p=0.13) compared to asymptomatic pts. In symptomatic group of pts, E' (p=0.004), PAP (p&lt;0.001) and GLS (p=0.04) significantly increased and LAɛ tended to decrease (p=0.18) during exercise. Age (r=−0.44, p=0.01), rE' (r=0.40, p=0.02), eE' (r=0.46, p=0.01), ePAP (r=−0.35, p=0.04) and LVWT (r=−0.32, p=0.07) significantly correlated with achieved METs in HCM pts overall. In multivariate analysis, eE' (β=0.60, 95% CI 0.122 to 0.009, p=0.003) was the only parameter independently correlated with exercise capacity (expressed in METs). Conclusions Symptomatic pts had a worse LV diastolic function (as expressed by E') and a severe LA longitudinal dysfunction (as expressed by LAɛ) during exercise. E' during exercise was the only parameter independently correlated with exercise capacity in pts with HCM. These suggest that a detailed analysis of LV and LA function during exercise could provide additional information to predict the occurrence of HF in HCM pts.

589P - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: Preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)

BackgroundFluoropyrimidines (FP) are the backbone chemotherapy (CT) for colorectal cancer (CRC). Although the most common toxicities have been extensively studied, FP-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity, still lacks of a comprehensive characterization. The correlation between FIC and known cardiovascular (CV) risk factors remains controversial and based on retrospective observations. MethodsCRC patients (pts) treated for the first time with FP at Candiolo Cancer Institute have been enrolled since January 2016. All pts were screened for potential CV risk factors; if needed, the treatment of preexisting CV comorbidities was optimized before starting CT. During the first 3 CT cycles, a monitoring with CV symptoms collection, seriated electrocardiograms and brain natriuretic peptide (BNP) measurements was performed. Primary objective was to assess the incidence of FIC. Secondary objectives included the analysis of the relationship of FIC with known CV risk factors and BNP levels. ResultsAn interim analysis was conducted on 101 pts (65% male, median age 71.6 years). We found high prevalence of CV risk factors (BMI ≥25 54.2%, smoker 50%, heavy drinker 23%, sedentary lifestyle 63.3%) and comorbidities (diabetes mellitus 19.2%, dyslipidemia 34.7%, arterial hypertension 54%, stroke 3%, coronary artery disease 6%, arrhythmias 8%, heart failure 4%). 19 pts (18.8%) experienced FIC: 1 acute coronary syndrome (ACS), 1 coronary vasospasm, 1 paroxysmal supraventricular tachycardia (PSVT), 1 complete left bundle branch block (LBBB), 2 syncope, 4 typical chest pain, 6 sudden dyspnea, 3 sudden palpitations. After treatment of the CV events, only 3 pts had to discontinue FP (ACS, LBBB and PSTV). Among symptomatic pts, only 47% had CV comorbidities and/or CV risk factors. BNP levels increased on average by 73% [CI 99%: +39% - +106%] after the first cycle. ConclusionsA high incidence of CV events, with no apparent correlation with CV comorbidities or risk factors, was observed. Prompt identification and treatment of CV events allowed most pts to complete the treatment with FP. Clinical trial identificationNCT02665312. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM. Aglietta: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

1361P - Outcomes of patients with melanoma brain metastases (MBM) treated with standard of care therapy after being excluded from MBM-specific clinical trials

BackgroundBrain metastases are a known complication of metastatic melanoma and often result in debilitating neurological conditions or death. Pts with MBM are typically excluded from trials, however, MBM-specific trials have been designed to assess the impact of systemic therapy in this challenging population. Combination immunotherapy has demonstrated a high rate of intracranial activity in pts with asymptomatic MBMs. However, many do not quallify during the screening period and never initiate protocol. We sought to determine the treatment patterns and therapeutic outcomes in pts considered for MBM-specific trials but screen failed before initiating treatment. MethodsWe reviewed the outcomes of pts considered for 2 MBM-specific trials that enrolled pts with untreated MBM at MD Anderson Cancer Center, CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Both studies had cohorts that allowed symptomatic pts or pts requiring steroids. We performed a retrospective medical record review of pts who failed screening to CM204 and BEAT-MBM. ResultsWe initially screened 65 pts and 38 screen-failed: 17 pts (50%) for BEAT-MBM and 21 pts (68%) for CM204. Of these, 15 received Ipi, Nivo, or combination off study. 5 (33%) responded to treatment and have maintained response. 10 pts received Ipi + Nivo and 3 (30%) of these maintained durable responses. 2 received Ipi alone (13%) and 3 received Nivo alone (20%). All pts received systemic therapy before radiation. Of the 5 responders, 2 received WBXRT after Ipi + Nivo. The remaining 23 pts received either targeted therapy (6), radiation alone (2), other immunotherapy +/- radiation (3), or no treatment (12). ConclusionsGiven the limited number of trials available to pts with MBM and high rate of screen failure (over 50% in our population), there is an unmet need that needs to be addressed. Of those patients that fail screening, many are eligible for systemic therapy off protocol. Pts with MBM treated with Ipi + Nivo off study still experienced therapeutic benefit. Given the high rate of screen failure in pts with MBM, there is a need for modification for eligibility criteria and the screening process to expedite on-protocol therapy in this vulnerable population. Clinical trial identificationCheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Legal entity responsible for the studyThe University of Texas M.D. Anderson Cancer Center. FundingThe University of Texas MD Anderson Cancer Center, Bristol-Myers Squibb, Genentech. DisclosureI. Glitza Oliva: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array; Advisory / Consultancy, Research grant / Funding (self): BMS; Research grant / Funding (self): Merck. R.N. Amaria: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Array. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution): Reata; Research grant / Funding (institution): Novartis. P. Hwu: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Iovance Biotherapeutics; Shareholder / Stockholder / Stock options: Immatics; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Sanofi. M.A. Davies: Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy: Array Biopharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Oncothyreon; Research grant / Funding (self): Myriad Genetics; Research grant / Funding (self): Sanofi. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glaxosmithkline. All other authors have declared no conflicts of interest.

P1011Electrophysiological trends in Wolff-Parkinson-White patients: a 33 years follow-up study

Abstract Background The Wolff-Parkinson-White (WPW) syndrome can be associated with sudden cardiac death, therefore risk assessment (RA) with electrophysiological (EP) testing (EPT) is mandatory to identify patients (pts) requiring catheter ablation (CAb). Our retrospective cohort study aimed to evaluate the variability of EP parameters during follow-up of WPW pts and the reliability of trans-esophageal EPT (TEEPT) for RA, evaluation of treatment efficacy, and EP follow-up of untreated athletes/pts. Method Data of 335 WPW pts, studied with TEEPT between 1985 and 2018, were retrospectively analyzed. Anterograde effective refractory period (ERP) of accessory pathways (AP) and of the atrioventricular node, Wenckebach point, shortest preexcited RR intervals (SPERRI) during atrial fibrillation (AF) and/or atrial pacing (At-P) and inducibility of supraventricular arrhythmias were assessed, at rest (supine and standing) and during effort. An AP was defined at high arrhythmogenic risk (HAR) if the anterograde AP-ERP and/or SPERRI (in AF or At-P) were ≤240 ms at rest or ≤200 ms during effort test. All patients were followed-up as outpatients or telephonically, as clinically required. 195 pts (17% female) were included, having exhaustive clinical information, two or more TEEPT and exhaustive clinical follow-up until late 2018. Time-evolution of EP parameters was evaluated, using parametric and non-parametric tests, as appropriate. Results and discussion Median age at first TEEPT was 20 years (IQR 16–29 years). Median follow- up was 44.3 months (IQR 16.4–122.9 months). Two pts (both identified at HAR and scheduled for surgery when ablation was unavailable) died suddenly, at rest. No other serious arrhythmic complication occurred, during the FU. Out of 19 pts (9.7% - Group A) showing enhanced AP conductivity at follow-up (mean ERP/SPERRI shortening: 30.8 ms, range 10–80 ms), 4 pts were found at HAR and underwent CAb. 176 pts (90.3% – Group B) showed a stable or impaired (25% under pharmacological treatment) AP conductivity during the follow-up. Their mean ERP/SPERRI increase was 39.7 ms (range 0–130 ms). Group A pts were significantly younger (20 vs 28 years old; 88% of Group A pts were &lt;30 years old) and more frequently male (94.1% vs 80.6%). A non-significant trend toward Group A was found for antero-septal APs (35% Group A vs 15.4% Group B). Conclusions TEEPT is a safe, non-invasive tool to stratify arrhythmogenic risk of WPW pts. Our data suggest that a watchful waiting is safe for low to moderate risk pts. Younger males with an antero-septal Kent bundle may deserve a more intensive EP follow-up. Aggressive therapy should be considered as mandatory only for symptomatic HAR pts, taking into account complications, risk/benefit ratio and pts' preferences. In other cases, medical therapy and watchful observation could be applied safely under periodical TEEPT, as appropriate.

173. Defining symptomatic versus radiographic distal junctional kyphosis after cervical deformity-corrective surgery

BACKGROUND CONTEXT Distal junctional kyphosis (DJK) is a relatively new surgical concept often defined in the literature as a change in DJK angle PURPOSE To establish a clinically relevant definition of symptomatic DJK. STUDY DESIGN/SETTING Retrospective review of a prospective CD surgery database. PATIENT SAMPLE One hundred and two patients with cervical deformity. OUTCOME MEASURES Demographics, HRQL metrics. METHODS A prospective database of operative CD patients was analyzed. Inclusion criteria were cervical kyphosis >10˚, cervical scoliosis >10˚, cSVA >4cm or CBVA >25˚. DJK angle (DJKA) was defined >10° change in kyphosis between LIV and LIV-2 in addition to >10° index angle. Pts with DJKA >10° & 1) no reop due to DJK(DJF) & 2) no physician-reported neurological sequelae at any time-point up to 1yr were categorized as “mild DJK.” Those with a DJKA >10° in addition to 1) reop due to DJK(DJF) or 2) >1 new-onset neurological sequelae related to DJK (spinal cord deficit, gait disturbance, hyperreflexia, lower-limb spasticity) were categorized as “Symptomatic DJK.” ANOVA explored differences in PROMs (NDI, mJOA, EQ5D, EQ5DVAS, NRS) at baseline (BL) up to 1yr follow-up. Multivariate logistic regression analyzed predictors of inferior HRQLs associated with DJK groups, specifically scoring beyond one standard deviation (SD) of the mean value of all DJK pts. RESULTS One hundred and two CD patients were analyzed. Sixty-five pts had no DJK, 25 pts had mild DJK and 12 pts had symptomatic DJK. By 1 year, 6/12 pts had DJF, 6/12 pts had >1 DJK-related neurologic sequelae not present before surgery(20% corticospinal tract deficit, 20% spasticity, 20% gait impairment, 20% hyperreflexia) without DJF, and 2 pts had both. Symptomatic DJK pts had higher mean DJKA than mild DJK pts immediately postop (29.8° vs 19.1°, p=0.150). No differences in BL HRQLs were noted between groups, including NDI, mJOA, EQ5D, VAS, and NRS Back (all p>0.05). At 1yr, Symptomatic DJK pts had significantly higher disability (52.3 vs 28.7, p=0.006) and trended lower EQ5D scores (0.75 vs 0.81, p=0.059), higher NRS back pain (5.82 vs 4.06, p=0.119), lower VAS (56.4 vs71.7,p=0.084), and lower mJOA (14.2 vs 15.0,p=0.495) than their mild DJK counterparts. Controlling for age and gender, conditional forward regression analysis revealed symptomatic DJK to a strong predictor of NDI >1 SD of the mean compared to mild DJK pts (OR: 43.4 [2.8 - 668.1], p=0.007); that is, symptoDJK increased the odds of NDI>1SD by at least 2.8x in relation to the mild DJK cohort. CONCLUSIONS DJK associated with reoperation and/or neurologic sequelae was associated with inferior quality of life metrics over long-term follow-up. Our results demonstrate that Symptomatic DJK may not necessarily correlate to a greater measured DJK angle per se (ie, >20°); instead, DJK with concurrent neuro findings or subsequent reop better predicts worsened disability compared to DJK alone. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC; CheckMate 650).

142 Background: Immune checkpoint inhibitor monotherapy has shown limited clinical benefit in patients (pts) with prostate cancer, likely due to an immunologically “cold” tumor microenvironment. We report preplanned interim efficacy/safety for NIVO + IPI in pts with mCRPC from CheckMate 650. Methods: Asymptomatic/minimally symptomatic pts who progressed after 2nd-generation hormone therapy and have not received chemotherapy for mCRPC (cohort 1) and pts who progressed after taxane-based chemotherapy (cohort 2) were included. Treatment was NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 doses, then NIVO 480 mg every 4 weeks. Coprimary endpoints: objective response rate (ORR) and radiographic PFS per PCWG2. Safety is a secondary endpoint. Exploratory endpoints include correlation of biomarkers with efficacy. Results: 78 pts had a minimum follow-up of 6 months; among pts with baseline measurable disease, ORR was 26% and 10% in cohorts 1 and 2 (Table). In both cohorts, ORR was higher in pts with PD-L1 ≥1%, DNA damage repair (DDR), homologous recombination deficiency (HRD), or above-median tumor mutational burden (TMB). Of all PSA responding pts (Table), 4 had PSA &lt;0.2 ng/mL. Grade 3–4 treatment-related adverse events occurred in 39% and 51% of pts in cohorts 1 and 2; one grade 5 event occurred in each cohort. Conclusions: In a malignancy where immune checkpoint inhibitor monotherapy has previously shown limited success, NIVO + IPI demonstrated activity in pretreated pts with mCRPC, particularly in a biomarker-enriched population, with a safety profile consistent with this dosing schedule. Further study is warranted. Clinical trial information: NCT02985957. [Table: see text]

Impact on MPN Symptoms and Quality of Life of Front Line Pegylated Interferon Alpha-2a Vs. Hydroxyurea in High Risk Polycythemia Vera and Essential Thrombocythemia: Results of Myeloproliferative Disorders Research Consortium (MPD-RC) 112 Global Phase III Trial

Impact on MPN Symptoms and Quality of Life of Front Line Pegylated Interferon Alpha-2a Vs. Hydroxyurea in High Risk Polycythemia Vera and Essential Thrombocythemia: Results of Myeloproliferative Disorders Research Consortium (MPD-RC) 112 Global Phase III Trial

Ruxopeg, a Multi-Center Bayesian Phase 1/2 Adaptive Randomized Trial of the Combination of Ruxolitinib and Pegylated Interferon Alpha 2a in Patients with Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis

BackgroundMPN-associated myelofibrosis (MF) is a condition characterized by splenomegaly, anemia, bone marrow (BM) fibrosis and debilitating symptoms. About 80% of patients (pts) harbor a driver mutations in JAK2, CALR or MPL genes that can be used as biomarkers for minimal residual disease assessment. Ruxolitinib (Rux) is a JAK inhibitor approved in intermediate or high risk (HR) MF to improve symptoms and splenomegaly but with little impact on the malignant clone and fibrosis. Interferon alpha (IFNa) can reduce mutant allele burden and fibrosis but is often poorly tolerated in highly symptomatic pts. The RUXOPEG study was designed to assess the efficacy and safety of the combination of Rux + IFNa in MF (NCT02742324).MethodsRUXOPEG is a multi-center Bayesian Phase 1/2 adaptive trial. Phase 1 includes up to 9 cohorts of 3 pts with increasing doses of both drugs. Tested doses of Rux and IFNa are 10, 15 and 20 mg BID, and 45, 90 and 135 mcg/week, respectively. Phase 2 will randomize between the 2 best dose combinations selected from phase 1. Primary objective: identify the most efficacious dose combination that also satisfies safety requirements. Primary tolerance criterion is the occurrence of dose limiting toxicities (DLT) within 45 days; primary efficacy criterion is >50% reduction in spleen length within 6 months. Secondary objectives include molecular response, reduction of BM fibrosis, quality of life and symptoms evolution, event-free and overall survival. The planned total enrollment is 42 pts. Key inclusion criteria are: diagnosis of MF (WHO criteria), intermediate or HR (IPSS), need of active therapy, presence of a driver mutation. Key exclusion criteria: prior treatment (or contra-indication) with Rux or IFNa, eligibility for stem cell transplantation, inadequate liver, cardiac or renal function, autoimmune disease, history of depression.Enrolment in 5 cohorts was completed in June 2018, and the last cohort for phase 1 will be opened in August. This abstract reports the current available data for the 5 cohorts who have completed the primary endpoint, but the presentation will provide the detailed analysis of primary and secondary endpoints of phase 1, which will be available in October 2018.ResultsAmong the 15 pts currently enrolled in phase 1, 6 were females, mean age was 60.9 years (range: 38-72), 8 had primary MF, 5 post ET and 2 post PV MF. Median spleen size was 6 cm (range 0 - 18) by palpation and 18 cm (range 10-25) by imaging. Mean (range) blood counts were: hemoglobin 12 g/dL (8.5 - 13.8), WBC 18.3 G/L (8 - 35.5), platelets 457 G/L (157 - 906) and 6 pts had circulating blasts. 12 pts had JAK2V617F and 2 had CALR mutations; karytotype was normal in 9 pts, abnormal in 5 (very HR in 3). In 10 pts analyzed by NGS so far, 8 had additional mutations (1 in 5 pts, 3 in 1, and 4 in 2) in TET2 (n= 5), ASXL1 (4), DNMT3A (2), TP53 (2), SF3B1 (1) and SRSF2 (1) genes.Safety: No DLT was observed in the 5 cohorts (primary safety criterion), the highest tested dose combination being Rux 15 mg BID + IFNa 135 mcg/week. The last cohort will test Rux 20 mg BID + IFNa 135 mcg/week. 4 serious adverse events have been reported: 1 AML transformation (very HR cytogenetics, 3% circulating blasts at baseline), 1 thrombotic event, 1 squamous cell carcinoma and 1 aggravation of Raynaud's phenomenon.Efficacy: preliminary data show a clear decrease in spleen size at 6 months (median 0 cm by palpation, range 0-9; 12.1 cm by imaging, range 10-21) and improvement in blood counts (mean, range): hemoglobin 10.5 g/dL (9.7 - 12.5), WBC 8.6 G/L (5.4 - 11.1), platelets 267 G/L (80 - 486). According to IWG criteria, all the 10 pts evaluable at time of abstract preparation responded (3 partial response, 7 hematological improvement). JAK2V617F allele burden decreased from a mean of 75% (range 43- 96) at baseline to 46% (range 24 - 84) at 6 months. Encouraging results were also found in a patient with 5 mutations (figure1) with a clear decrease in JAK2V617F, ASXL1, DNMT3A and EZH2 mutations after 12 months of treatment.ConclusionRUXOPEG is the first study to formally assess the safety and efficacy of Rux + IFNa combination in MF patients never exposed to either drugs before. The first 5 dose combinations tested showed no DLT, confirming that this combination was generally well tolerated. Preliminary efficacy results are encouraging, including in patients who received very low doses of both drugs. Full results of the 6 cohorts tested in phase 1 and doses selected for phase 2 will be presented. DisclosuresKiladjian:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Giraudier:Novartis: Research Funding. Cassinat:Novartis: Research Funding; AOP Orphan: Research Funding.

Abstract P6-03-06: Assessing occult brain metastasis with CT scan or MRI in HER2-positive breast cancer patients at initial diagnosis

Abstract Patients (pts) with HER2-positive breast cancer (BC) have a high risk of developing brain metastases (BM) that might be due to longer survival, low diffusion of Trastuzumab (T) in the CNS or an unknown incidence of occult BM at diagnosis. In a series of metastatic BC, occult metastasis was found in 15 % of the patients and Her2 over expression was an independent risk factor 1.In a series of early BC treated with T the cumulative incidence of BM at 12 and 24 months was 0.6 and 2 % respectively 2. Time to BM was 13.7 months in retrospective study 3 . Systematic cranial magnetic resonance imaging (MRI) in the staging of HER2-positive BC pts detected BM in 22 % of asymptomatic, metastatic pts versus 3.6 % in asymptomatic, non-metastatic pts 4. Early detection of BM decreases the cerebral death rate, but do not prolong survival in metastatic pts 4 . Therefore brain imaging is not recommended at diagnosis. However, retrospective trials assessing the incidence of BM in HER2-positive BC were mainly performed during follow up and not at the initial diagnosis. Pts treated for HER2-positive locally BC with adjuvant sequential chemotherapy including anthracycline and taxane associated with T, classified according to classical prognosis factor as histological subtype, TNM, SBR and hormonal receptor (HR), were systematically assessed for occult BM at initial diagnosis with CT scan or MRI. Retrospectively analyzed for the occurrence of BM was performed. Disease free metastatic survival (DFMS) and overall survival (OS) was estimated by Kaplan Meier estimation. Between March 2006 and July 2013 84 pts were included. The median follow up is 4.7 years. The characteristics pts were median age 57 years [30-86], ductal carcinoma 67 pts (93 %), lobular carcinoma 5 pts (7%), pT1 to 4 respectively 38 (48 %), 28 (36 %), 3 (4%), 9 pts (12%), pN 0 to 3 respectively 44 (54%), 27 (33%), 5 (6%), 5 pts (6%), SBR 1 to 3 respectively 1 (1%), 35 (43%), 43 pts (54%), RO positive 47 pts (59 %), RP positive 27 pts (63%). Thirty eight pts (45 %) had brain imaging at diagnosis or within 5 months of diagnosis. Only one pt with a pT4, pN2, ductal carcinoma, RO+, RP-, SBR 2 presented with BM (2.6 %) at initial diagnosis, with simultaneous lung, liver, bone and nodes metastasis. Four pts (4.8 %) presented BM during follow up, among those two symptomatic pts (2.4 %) as the only site of recurrence at 21 and 28 months. Median DFMS was 8.5 years and median OS was 16.7 years. This is the first report of systemic imaging at initial diagnosis of HER2 positive locally BC pts. The results did not support initial brain imaging in this subset of pts. Only pts with symptoms seems to benefit from brain imaging. Further prospective study should be launched to confirm this observation. Citation Format: Delbaldo C, Sarrade T, Brieau B, Billemont B, Denis J, Cojean-Zelek I, Bornier C, Vincens E. Assessing occult brain metastasis with CT scan or MRI in HER2-positive breast cancer patients at initial diagnosis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-06.

Novel Evidence-Based Diagnosis, Classification and Management of Lower Extremity Deep Vein Thrombosis (DVT), Prevention of DVT Recurrence and the Post-Thrombotic Syndrome: Personal Experiences and Critical Appraisal of the Literature 1998-2018

Background: Two point CUS (2-CUS) for the diagnosis of symptomatic proximal DVT overlooks calf vein thrombosis (CVT) indicating the need to repeat 2-CUS after one week, which is not cost-effective. Complete CUS (CCUS) of all deep veins from the groin to the ankle in a single procedure will pick up CVT, proximal DVT and isolated ileo femoral DVT plus alternative diagnoses, which is cost-effective. Methodology: We evaluated the combined use of non-invasise 2-CUS versus complete compression ultrasonography (CCUS) and quantitative Elisa D-dimer levels (500, 1000 and 1500 ng/mL) in prospective large management studies between 1998 and 2018 in view of the literature on DVT diagnosis and prevention of DVT recurrence and the post-thrombotic syndrome. Results: Complete compression ultrasonography (CCUS) followed by a sensitive D-dimer test and clinical score assessment is a safe and cost-effective non-invasive strategy to exclude and diagnose deep vein thrombosis (DVT) and alternative diagnoses (AD) in patients with suspected DVT. Rapid and complete recanalization on serial CUS within 3 months post-DVT with no residual venous pathology (RVP-) is associated with low risk of DVT recurrence (1.2% patient/years) and PTS on the basis of which both anticoagulation MECS can be withdraw at 4 months postDVT. Delayed and incomplete recanalization with RVP+ on CUS at 3 months post-DVT is associated with the presence of reflux due to valve destruction, a high risk of DVT recurrence. Symptomatic PTS at 6 to 12 months postDVT have a clear indication to wear MECS for symptomatic relief of PTS symptoms and to extend anticoagulation for one to several years to prevent DVT recurrence. Wearing MECS does not prevent DVT recurrence, reflux and outlet obstruction in symptomatic PTS patients in the original Prandoni and the two large COX and IDEAL prospective randomized clinical studies. The Lower Extremity Thrombosis (LET) extension classification identifies patients with CVT LET class I, proximal DVT LET class II and iliofemoral DVT LET class III at time of acute DVT diagnosis. The higher the LET class the higher the risk of DVT recurrence and PTS. Conclusion: The Villalta score for PTS is not sensitive and specific enough to stratefy for DVT recurrence risk for the indication of extended anticoagulation in post-DVT patients after discontinuation of anticoagulation. Wearing MECS relieves subjective signs of PTS, does not reduce DVT and PE recurrence rate and has no influence on the natural history of PTS. The two randomized clinical trials CaVent and ATTRACT comparing catheter directed thrombolysis followed by anticoagulation versus anticoagulation alone were neither inferior nor superior to anticoagulation for the treatment of acute proximal popliteal-femoral and iliofemoral DVT.