The results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer are reported. There were no statistically significant changes in GLS, and TnI and BNP levels. The finding supports the cardiac safety of THP in this group of patients.
Objectives
To evaluate 1) the prognostic implication of baseline global longitudinal strain (GLS) and 2) the added value of GLS beyond the circulating cardiac biomarkers for risk stratification in patients with light chain (AL) amyloid undergoing autologous hematopoietic cell transplant (HCT).
Background
Autologous HCT is a first line therapy for prolonging survival in patients with AL amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT due to high risk of transplant related mortality and poor overall survival. Whether GLS can provide additional risk stratification and predict survival after HCT in this high risk population remains unclear.
Methods
82 patients with newly diagnosed AL amyloidosis who underwent upfront HCT between January 2007 to April 2014 were included in the study. Clinical, echo and serum cardiac biomarker data were collected at baseline and 12 months following HCT. GLS measurements were performed using a vendor independent offline system. The median follow-up time for survivors was 58 months.
Results
64% of the patients were in biomarker based Mayo stage II or III. GLS, BNP, troponin and mitral E/A ratio were identified as the strongest predictors of survival (p<0.0001). Other predictors included sex, creatinine, free light chain, wall thickness and EF. The Mayo stage was significantly associated with outcome with 5 year survival of 93%, 72% and 31% in stage I, II and III patients, respectively. A GLS of 17% was identified as the value which best discriminated survivors from non-survivors and the application of this cutoff value provided further mortality risk stratification within each Mayo stage.
Conclusions
GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over the serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with the serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies.
BackgroundCardiac magnetic resonance (CMR) imaging is well validated for tissue characterization of cardiac masses but has not been applied to study pattern and prognostic implications of cardiac metastases (CMETs) among patients with systemic cancer.Methods and ResultsThe population consisted of 60 patients with stage IV cancer (32 patients with CMETs, 28 diagnosis‐matched controls) undergoing CMR. CMET was defined as a discrete mass with vascular tissue properties on delayed enhancement CMR. CMET‐positive patients and controls had similar clinical characteristics, cardiac geometry, and function (P=NS). Leading cancer types associated with CMET were sarcoma, melanoma, and gastrointestinal. Patients with CMETs had similar distribution of extracardiac metastatic disease compared with controls (organs involved: 3.4±2.0 versus 2.7±1.9, P=0.17). In 94% of patients with CMETs, there were metastases involving ≥1 extracardiac organ (66% lung involvement). CMET location varied (right ventricle 44%, right atrium 19%, left ventricle 28%, left atrium 9%, pericardial 25%); 22% of cases had multichamber involvement. Right‐sided chamber involvement was common in hematologic/lymphatic spread (67%); pericardial involvement was common with direct spread (64%). Regarding tissue properties on delayed enhancement CMR, CMETs commonly (59%) demonstrated heterogeneous enhancement (41% diffuse enhancement). Heterogeneous lesions were larger and had increased border irregularity (P<0.05). Survival 6 months post‐CMR was numerically lower among patients with CMETs (56% [95% CI 39–74%]) versus stage IV cancer–matched controls (68% [95% CI 50–86%]), although differences between groups were nonsignificant (P=0.42).Conclusions
CMETs vary regarding etiology, location, and tissue properties on CMR, highlighting need for comprehensive surveillance of cardiac involvement regardless of cancer origin. Prognosis remains poor with for patients with CMETs, albeit similar to that for stage IV cancer controls matched for cancer etiology.
BackgroundLate gadolinium enhancement (LGE-) cardiovascular magnetic resonance (CMR) is well-validated for cardiac mass (CMASS) tissue characterization to differentiate neoplasm (CNEO) from thrombus (CTHR): Prognostic implications of CMASS subtypes among systemic cancer patients are unknown.MethodsCMASS + patients and controls (CMASS -) matched for cancer diagnosis and stage underwent a standardized CMR protocol, including LGE-CMR (IR-GRE) for tissue characterization and balanced steady state free precession cine-CMR (SSFP) for cardiac structure/function. CMASS subtypes (CNEO, CTHR) were respectively defined by presence or absence of enhancement on LGE-CMR; lesions were quantified for tissue properties (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR) and size. Clinical follow-up was performed to evaluate prognosis in relation to CMASS etiology.ResultsThe study population comprised 126 patients with systemic neoplasms referred for CMR, of whom 50% (n = 63) had CMASS + (CNEO = 32%, CTHR = 18%). Cancer etiology differed between CNEO (sarcoma = 20%, lung = 18%) and CTHR (lymphoma = 30%, GI = 26%); cardiac function (left ventricular ejection fraction: 63 ± 9 vs. 62 ± 10%; p = 0.51∣ right ventricular ejection fraction: 53 ± 9 vs. 54 ± 8%; p = 0.47) and geometric indices were similar (all p = NS). LGE-CMR tissue properties assessed by CNR (13.1 ± 13.0 vs. 1.6 ± 1.0; p < 0.001) and SNR (29.7 ± 20.4 vs. 15.0 ± 11.4, p = 0.003) were higher for CNEO, consistent with visually-assigned diagnostic categories. CTHR were more likely to localize to the right atrium (78% vs. 25%, p < 0.001); nearly all (17/18) were associated with central catheters. Lesion size (17.3 ± 23.8 vs. 2.0 ± 1.5 cm2; p < 0.001) was greater with CNEO vs. CTHR, as was systemic disease burden (cancer-involved organs: 3.6 ± 2.0 vs. 2.3 ± 2.1; p = 0.02). Mortality during a median follow-up of 2.5 years was markedly higher among patients with CNEO compared to those with CTHR (HR = 3.13 [CI 1.54–6.39], p = 0.002); prognosis was similar when patients were stratified by lesion size assessed via area (HR = 0.99 per cm2 [CI 0.98–1.01], p = 0.40) or maximal diameter (HR = 0.98 per cm [CI 0.91–1.06], p = 0.61). CTHR conferred similar mortality risk compared to cancer-matched controls without cardiac involvement (p = 0.64) whereas mortality associated with CNEO was slightly higher albeit non-significant (p = 0.12).ConclusionsAmong a broad cancer cohort with cardiac masses, CNEO defined by LGE-CMR tissue characterization conferred markedly poorer prognosis than CTHR, whereas anatomic assessment via cine-CMR did not stratify mortality risk. Both CNEO and CTHR are associated with similar prognosis compared to CMASS - controls matched for cancer type and disease extent.
A high suspicion for relapsed metastatic disease must arise when an intracardiac mass is detected in a patient with a recent history of Ewing sarcoma. Nevertheless, the scenario may eventually turn out to be much more complex than expected, and the possibility that the intracardiac tumor may instead be a "second" primary sarcoma, although extremely rare, should also be considered. We describe the first case of concomitant diagnosis of Ewing sarcoma and low-grade myxoid spindle cell sarcoma in the same young patient.
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