Citations

Key Clinical Message Myxoinflammatory fibroblastic sarcoma is a rare sarcoma which typically presents in the extremities and is treated by definitive surgery. In recurrent disease, the reported utilization of radiotherapy is increasing, and more modern techniques such as intensity‐modulated radiotherapy may be improving long‐term outcomes.

367 Background: While neoadjuvant chemotherapy (NAC) for muscle−invasive bladder cancer (MIBC) is recognized as the standard of care, the management of patients with locally advanced and/or nodal disease after NAC and radical cystectomy (RC) is not well defined. We sought to evaluate the association of adjuvant chemotherapy (AC) and overall survival (OS) among patients with adverse pathology after NAC and RC. Methods: The National Cancer Database was reviewed to identify patients with adverse pathology (pT3N0, pT4N0, or pTanyN1−3) at RC following NAC from 2006−2012. Patients were stratified by receipt of AC. Clinical and pathologic variables were abstracted. OS was the primary end−point and differences on the basis of AC were assessed by the Kaplan−Meier method and log−rank test. Multivariable Cox proportional hazards regression was used to assess the association of AC with OS controlling for age, sex, race, Charlson score, year of diagnosis, pathologic stage, and receipt of adjuvant radiotherapy. Results: Adverse pathology following NAC and RC was identified in 1,361 patients from 2006−2012, of whom 328 (24.1%) received AC. Staging was pT3N0 in 444 (32.6%), pT4N0 in 162 (11.9%), and pTanyN1−3 in 755 (55.5%). Median OS for the entire cohort was 22.9 months, which differed by pathologic stage: 34.6 months (pT3N0), 21.4 months (pT4N0), and 19.3 months (pTanyN1-3)(p < 0.01). No difference in OS was noted by receipt of AC in the overall cohort (median OS 24.6 months with AC vs 22.0 months without AC; p = 0.18), or when stratified by pathologic stage. On multivariable analysis, receipt of AC was not significantly associated with overall mortality (HR 0.86; 95%CI 0.74−1.01; p = 0.06) for all patients. When stratified by stage, AC was associated with a significantly decreased risk of mortality among patients with pT4N0 disease (HR 0.56; 95%CI 0.33−0.97; p = 0.04), but not pT3N0 or pTanyN1−3 (p > 0.05). Conclusions: Patients with adverse pathology at RC after NAC have a median OS of approximately 2 years. AC was not associated with improved survival, except in the subgroup with pT4N0 disease. Clinical trials with newer systemic therapies are warranted for patients in this setting.

Abstract Background:Anti-HER2 agents are associated with an increased risk of cardiotoxicity, occurring mostly during treatment and being generally reversible. To date, no cardiac biomarkers have been validated as predictive markers of cardiotoxicity in patients (pts) receiving anti-HER2 therapies. We evaluated high sensitivity (HS) troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pts treated with neoadjuvant anti-HER2 therapies to evaluate if early elevation of cardiac biomarkers predicts early or late cardiac events. Material and Methods: 455 pts were randomized to receive either lapatinib (154 pts), trastuzumab weekly (149 pts), or lapatinib with trastuzumab for a total of 6 weeks (152 pts). After this biological window, pts continued on the same targeted therapy plus 12-weekly paclitaxel until definitive surgery. After surgery, patients received adjuvant FEC (3x) followed by the same HER2 therapy as in the neoadjuvant phase for further 34 weeks (to complete 52 weeks in total). Eligible pts had an LVEF ≥50%. Cardiac biomarkers were centrally tested in plasma samples collected at baseline, week 2 (W2) and at surgery. Elevated biomarker was defined as either TNT &gt;0.015 μg/L or NT-proBNP &gt;125 pg/mL. The small number of pts and rarity of marker elevations allowed only descriptive analyses. Results: At a median follow-up of 3.8 years, 280 pts had cardiac biomarkers tested at baseline (61.5%) and NT-proBNP was elevated in 39 pts (13.9%) while TNT was elevated in only 1 pt (0.35%). From those 39 pts with NT-proBNP elevated at baseline, only 1 pt experienced a cardiac event. Also, hypertension was presented in 14 pts (24.5%) with elevated NT-proBNP. Serial measurements were available in 173 pts (61.7%) and NT-proBNP was elevated in 25, 10 and 21 pts at baseline, W2 and at surgery, respectively, while among 171 pts (61%) TNT was elevated in 1, 1 and 5 pts, respectively. There were 13 cardiac events in 11 pts in the entire trial. Five of these pts had a measurement of cardiac biomarkers at baseline (non-elevated NT-prBNP and TNT were observed in 4 and 5 pts), 9 of them had a measurement at week 2 (non-elevated NT-prBNP and TNT were observed in 8 and 9 pts) and 3 of them at surgery (non-elevated NT-prBNP and TNT were observed in 3 and 3 pts), respectively. The following table show the low specificity of the cardiac biomarkers. Patients without cardiac event (N)Patients with cardiac event (N)Patients with elevated markerElevated NT-proBNP Baseline38139Week 229130Surgery40040Elevated TNT Baseline101Week 2101Surgery606 During adjuvant phase, 13 pts experienced LVEF drop to &lt;50% and none had either NT-proBNP elevated or TNT at surgery. Conclusions: Despite the small sample size, we demonstrated that cardiac biomarkers are rarely elevated in pts receiving anti-HER2 therapies, which is probably due to the absence of myocyte necrosis with respect to TNT, and the lack of chamber dilation in the case of NT-proBNP after exposure to these drugs. In addition, few cardiac events were present in this population not previously exposed to anthracycline-based chemotherapy; therefore the use of cardiac biomarkers in this population may be unnecessary. Citation Format: de Azambuja E, Bradbury I, Ewer M, Campbell C, Zardavas D, Ameels H, Baselga J, Huober J, Izquierdo M, Bozovic-Spasojevic I, Maetens M, Harbeck N, Pusztai L, Piccart M, Rodeheffer R, Sutter T. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2 positive early breast cancer (BIG 1-06) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-09.

445 Background: Radical cystectomy (RC) is the gold standard treatment for muscle-invasive and high-risk non-muscle invasive bladder cancer. However, the procedure has been associated with a high complication rate, including perioperative infection. In addition to resulting in patient morbidity, infections have been suggested as a quality metric. We sought to evaluate the incidence, risk factors, and timing of infection following RC. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried to identify patients undergoing RC for bladder cancer from 2005-2013 using CPT procedure and ICD-9 diagnosis codes. Infections (urinary tract infection (UTI), surgical site infection (SSI), and sepsis) within 30 days of RC were recorded. Characteristics including age, gender, ethnicity, body-mass index, diabetes, smoking status, renal function, steroid usage, albumin, receipt of perioperative transfusion, and operative time were abstracted, and relative risk of infection was assessed in univariate chi-squared analysis. Results: A total of 3,187 patients were identified, of whom 2604 (81.8%) were male, with a median age of 68.8 years (IQR 62, 77). Postoperative infection was diagnosed in 766 (24%) patients, at a median of 13 days (IQR 8, 19) after RC, with 44.4% occurring prior to hospital discharge. The most common type of infection was SSI (404; 12.7%), followed by sepsis (315; 9.9%), and UTI (309; 9.7%). Factors associated with increased overall infection risk were obesity (RR 1.32; 1.20-1.46; p < 0.001), receipt of a blood transfusion (RR 1.20; 1.10-1.31; p < 0.001), and increased operative time (RR for > 450 min 1.46; 1.26-1.70; p < 0.001). Risk factors for UTI in particular included obesity (RR 1.28; 1.11-1.47; p < 0.001), diabetes (RR 1.38; 1.09-1.75; p = 0.009), and increased operative time (RR for > 450 min 1.45; 1.18-1.78; p < 0.001). Conclusions: Approximately 25% of patients undergoing RC experience an infection within 30 days of surgery, most commonly SSI. Several modifiable risk factors were identified, including blood transfusion and prolonged operative time, that represent potential targets for care improvement.

BackgroundSyncope is a common reason for outpatient transthoracic echocardiography (TTE). We studied the applicability of pediatric appropriate use criteria (AUC) on initial outpatient evaluation of children (≤18 years) with syncope.MethodsData were obtained before (Phase I, April–September 2014) and after (Phase II, January‐April 2015) the release of the AUC document from six participating pediatric cardiology centers. Site investigators determined the indication for TTE and assigned appropriateness rating based on the AUC document: Appropriate (A), May Be Appropriate (M), Rarely Appropriate (R), or “unclassifiable” (U) if it did not fit any scenario in the AUC document.ResultsOf the total 4562 TTEs, 310 (6.8%) were performed for syncope: 174/2655 (6.6%) Phase I and 136/1907 (7.1%) Phase II, P=.44. Overall, 168 (50.5%) were for indications rated A, 63 (18.9%) for M, 79 (23.7%) for R, and 23 (6.9%) for U. Release of AUC did not change the appropriateness of TTEs [A=51.6% vs 49.0%, P=.63, R=20.2% vs 28.3%, P=.09]. Overall syncope‐related R indications formed 15.7% of R indications for all the echocardiograms performed in the entire Pediatric Appropriate Use (PAUSE) study (11.9% Phase I and 22.4% Phase II, P=.002). TTEs were normal in majority of the patients except 7 that had incidental findings.ConclusionsIn conclusion, syncope is a common reason for indications rated R and release of the AUC document did not improve appropriate utilization of TTE in syncope. Targeted educational interventions are needed to reduce unnecessary TTEs in children with syncope.

Objective This study sought to estimate the prevalence of median lingual lymph node (MLLN) metastases from oral cavity squamous cell carcinoma (OCSCC) and determine the frequency with which MLLNs can be identified with magnetic resonance imaging (MRI) in control subjects. Methods Pathology reports were used to identify patients with surgically treated OCSCC who underwent preoperative positron emission tomography–computed tomography to define the prevalence of MLLN metastases. As a control group, 500 consecutive face-neck MRIs from noncancer patients were reviewed for structures consistent with MLLNs. Results In the study group, 1 (0.95%) of 105 OCSCC cases demonstrated a single MLLN metastasis from a lateral tongue tumor (T4aN2c). The MLLN exceeded 1 cm in all planes and was abnormal in morphology. The frequency of suspected MLLNs in controls was 1.0%, with a maximum measurement of 0.9 cm. Conclusions Median lingual lymph nodes are infrequently identified with MRI in controls, concordant with the low prevalence of metastases from OCSCC to this inconstant nodal group.

Cardiac output (CO) assessment as a basic hemodynamic parameter has been of interest in exercise physiology, cardiology, and anesthesiology. Noninvasive techniques available are technically challenging, and thus difficult to use outside of a clinical or laboratory setting. We propose a novel method of noninvasive CO assessment using a single, upper-arm cuff. The method uses the arterial pressure pulse wave signal acquired from the brachial artery during 20-s intervals of suprasystolic occlusion. This method was evaluated in a cohort of 12 healthy individuals (age, 27.7 ± 5.4 yr, 50% men) and compared with an established method for noninvasive CO assessment, the open-circuit acetylene method (OpCirc) at rest, and during low- to moderate-intensity exercise. CO increased from rest to exercise (rest, 7.4 ± 0.8 vs. 7.2 ± 0.8; low, 9.8 ± 1.8 vs. 9.9 ± 2.0; moderate, 14.1 ± 2.8 vs. 14.8 ± 3.2 l/min) as assessed by the cuff-occlusion and OpCirc techniques, respectively. The average error of experimental technique compared with OpCirc was −0.25 ± 1.02 l/min, Pearson’s correlation coefficient of 0.96 (rest + exercise), and 0.21 ± 0.42 l/min with Pearson’s correlation coefficient of 0.87 (rest only). Bland-Altman analysis demonstrated good agreement between methods (within 95% boundaries); the reproducibility coefficient (RPC) = 0.84 l/min with R2= 0.75 at rest and RPC = 2 l/min with R2= 0.92 at rest and during exercise, respectively. In comparison with an established method to quantify CO, the cuff-occlusion method provides similar measures at rest and with light to moderate exercise. Thus, we believe this method has the potential to be used as a new, noninvasive method for assessing CO during exercise.