Response rates in metastatic neuroendocrine tumors receiving peptide receptor radionuclide therapy and implications for future treatment strategies

BackgroundPeptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies.MethodsWe retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and ⁶⁸Ga-DOTATATE-positron emission tomography before and after 2 or 4 cycles of peptide receptor radionuclide therapy. Tumor response was evaluated by RECIST 1.1. Statistics included multinomial logistic regression models and Fisher exact test.ResultsTwenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%).ConclusionPatients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.     

Clinical implications of increased lung uptake of thallium-201 during exercise scintigraphy 2 weeks after myocardial infarction

To determine the prevalence and clinical significance of increased lung thallium-201 uptake during submaximal exercise myocardial scintigraphy performed 2 weeks after acute myocardial infarction, 61 patients underwent submaximal exercise testing (target heart rate, 120 beats/min), multigated blood pool imaging at rest and coronary angiography before hospital discharge. Thallium lung uptake on the initial anterior projection image was graded qualitatively by comparing the intensity of thallium-201 activity in the lungs with that in the mediastinum. In 39 patients (64 percent), it was normal (equal to mediastinal activity) and in 22 (36 percent), it was increased (greater than mediastinal activity). Compared with patients with normal lung uptake, those with increased uptake had a greater prevalence of prior infarction (13 versus 36 percent, probability [p] < 0.05), less global cardiac reserve as assessed by the four level New York Heart Association classification (p < 0.05), more advanced Killip class in the coronary care unit (p < 0.05), a higher Norris coronary prognostic index (2.6 ± 1.9 versus 4.6 ± 2.3 [mean ± standard deviation], p <0.01), failure to achieve the target heart rate because of dyspnea, fatigue or angina (36 versus 86 percent, p < 0.01), a greater prevalence of exercise-induced S-T segment depression (18 versus 45 percent, p < 0.05), a greater number of anterior thallium-201 myocardlal defects (p < 0.05); a lower radionuclide ejection fraction at rest (50.4 ± 6.1 versus 39.6 ± 9.3 percent, p < 0.01) and a greater number of asynergic left ventricular segments (p < 0.05).Thus, the occurrence of increased lung thallium-201 uptake during submaximal exercise scintigraphy in the early postinfarction period is frequent and appears to be a marker of severe and functionally more important coronary artery disease associated with left ventricular dysfunction.     

Management of the elderly aortic stenosis patient with low gradient and low ejection fraction

The incidence of aortic stenosis increases with age and thus it occurs frequently in elderly patients. Once severe obstruction has developed, death occurs within 3 years unless the aortic valve is replaced. The results of aortic valve surgery, even in octogenarians, are usually excellent in the absence of comorbidity. The exception to this rule is for the aortic stenosis patient who has low ejection fraction, a low cardiac output and a transvalvular gradient of <30 mm Hg. Such patients have far advanced left ventricular dysfunction and increased operative mortality. However, even these patients may benefit from surgery if they have truly severe aortic stenosis. Because valve area is unreliable at low cardiac outputs, output should be increased pharmacologically in such patients and the valve area recalculated. If the transvalvular gradient increases with output, severe aortic stenosis is present and valve replacement may be beneficial. However, if output increases but gradient does not, only mild stenosis is present and surgery is unlikely to prolong life.     

Interventions to Improve Care Related to Colorectal Cancer Among Racial and Ethnic Minorities: A Systematic Review

Objective

To systematically review the literature to identify interventions that improve minority health related to colorectal cancer care.

Data sources

MEDLINE, PsycINFO, CINAHL, and Cochrane databases, from 1950 to 2010.

Study eligibility criteria, participants, and interventions

Interventions in US populations eligible for colorectal cancer screening, and composed of ??50?% racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). All included studies were linked to an identifiable healthcare source. The three authors independently reviewed the abstracts of all the articles and a final list was determined by consensus. All papers were independently reviewed and quality scores were calculated and assigned using the Downs and Black checklist.

Results

Thirty-three studies were included in our final analysis. Patient education involving phone or in-person contact combined with navigation can lead to modest improvements, on the order of 15 percentage points, in colorectal cancer screening rates in minority populations. Provider-directed multi-modal interventions composed of education sessions and reminders, as well as pure educational interventions were found to be effective in raising colorectal cancer screening rates, also on the order of 10 to 15 percentage points. No relevant interventions focusing on post-screening follow up, treatment adherence and survivorship were identified.

Limitations

This review excluded any intervention studies that were not tied to an identifiable healthcare source. The minority populations in most studies reviewed were predominantly Hispanic and African American, limiting generalizability to other ethnic and minority populations.

Conclusions and implications of key findings

Tailored patient education combined with patient navigation services, and physician training in communicating with patients of low health literacy, can modestly improve adherence to CRC screening. The onus is now on researchers to continue to evaluate and refine these interventions and begin to expand them to the entire colon cancer care continuum.     

New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility

BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α₁,β₁,β₂-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions.Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF_c). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF_c-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF_c relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months.ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.     

Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injection of exenatide (exendin-4) in healthy subjects

Exenatide is an incretin mimetic with potential glucoregulatory activity in type 2 diabetes. This randomized, single-blind, placebo-controlled 6-way crossover study assessed exenatide's effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at -1, 0, +1, +2, and +4 hours, relative to the 10 mug exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC(0-12 h) values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the -1-hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption.