Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

Optimal First-Line Therapy for Metastatic Adenocarcinoma of the Esophagus.

OPINION STATEMENT: Treatment strategies for esophageal adenocarcinoma patients continue to advance with the generation of more data from clinical trials that are permitting us to refine the use of immunotherapy in combination with other treatment modalities. While the frontline therapy for metastatic esophageal adenocarcinoma has become more complicated with the approval of combination regimens, it is also yielding better outcomes. These treatment strategies can now be individualized to fit patient circumstances and goals as well as the biomarker profile of their individual tumors leading to an increased likelihood of treatment related remissions and extended median survivals. Comprehensive genomic profiling at diagnosis should now be standard to allow the management team to customize each patient's treatment plan based on the genetic abnormalities discovered in their tumor. By refining these targeted approaches, we will see decreased toxicities and increased survival.

Successful use of phlebotomy to treat severe secondary polycythemia due to chronic lung disease.

Secondary polycythemia (SP) occurs as a result of increase erythropoietin levels most commonly as a result of tissue hypoxia. Symptoms such as erythromelalgia, pruritis, and bleeding, which are frequently seen in polycythemia vera (PV), do not commonly occur in SP. Phlebotomy is considered one of the mainstays of therapy for PV but is rarely used for treatment of SP due to concern about worsening tissue hypoxia. We present the case of a patient with severe SP due to chronic hypoxic lung disease who presented with erythromelalgia, pruritis, and bleeding and was treated successfully with therapeutic phlebotomy. This case illustrates the importance of considering the use of therapeutic phlebotomy in symptomatic patients with severe SP.

Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

INTRODUCTION: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. METHODS: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011-2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. RESULTS: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. CONCLUSIONS: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.

Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. OBJECTIVE: This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. METHODS: A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality. RESULTS: Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts. CONCLUSIONS: Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Gemcitabine and carfilzomib induced thrombotic microangiopathy: eculizumab as a life-saving treatment.

Drug-induced aHUS is rare; however, early diagnosis is vital to reduce morbidity and mortality. With confirmation of the diagnosis, eculizumab appears to be a viable treatment option to suppress the pro-inflammatory surge. Furthermore, adverse side effects of medications such as carfilzomib and gemcitabine should be considered in the appropriate settings.