A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer.

PURPOSE: Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016). MATERIALS AND METHODS: Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival. RESULTS: Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events. CONCLUSIONS: The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

Neoadjuvant Immune Checkpoint Inhibition in Metastatic Conjunctival Melanoma.

The development of immune checkpoint inhibitors (ICI) has transformed the treatment of advanced-stage cutaneous melanoma; however, most trials did not include patients with conjunctival melanoma. Herein the authors describe a patient with recurrent conjunctival melanoma who developed locally advanced, b-raf and v-raf murine sarcoma viral oncogene homolog B1-negative melanoma in her nasal cavity and extensive, metabolically active, bilateral lymphadenopathy in her thorax. Her nasal mass measured 4.3 × 1.7 cm and was determined to be unresectable. She was treated with 4 cycles of combination ipilimumab and nivolumab therapy followed by maintenance nivolumab. She experienced a dramatic treatment response with a reduction in the size of her nasal mass to 3.0 × 1.1 cm and a complete resolution of her adenopathy. She then underwent complete surgical resection of her residual mass (approximately 75% of her original tumor size) and remains melanoma-free at 1 year of follow-up. Given the underlying genetic similarities of conjunctival melanoma to cutaneous melanoma, providers should consider the use of neoadjuvant immune checkpoint inhibitors for patients with locally advanced or limited metastatic disease.

Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

Clinical Correlates of Benefit From Radium-223 Therapy in Metastatic Castration Resistant Prostate Cancer.

BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods. Bone Scan Index (BSI) was derived from available bone scans using EXINI software. RESULTS: One hundred and forty-five patients were included. Radium-223 was administered for six cycles in 74 patients (51%). One-year survival in this heavily pre-treated population was 64% (95%CI: 54-73%). In univariate and multivariate analysis, survival was highly associated with receiving all six doses of Radium-223. Receipt of six doses was associated with ECOG PS of 0-1, lower baseline PSA & pain level, no prior abiraterone/enzalutamide, <5 BSI value, and normal alkaline phosphatase. In patients who reported baseline pain (n = 72), pain declined in 51% after one dose and increased in 7%. PSA declined ≥50% in 16% (18/110). Alkaline phosphatase declined ≥25% in 48% (33/69) and ≥50% in 16/69 patients. BSI declined in 17 (68%) of the 25 patients who had bone scan available at treatment follow-up. Grade ≥3 neutropenia, anemia, and thrombocytopenia occurred in 4% (n = 114), 4% (n = 125), and 5% (n = 123), respectively. CONCLUSIONS: Patients earlier in their disease course with <5 BSI, low pain score, and good ECOG performance status are optimal candidates for radium-223. Radium-223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479-488, 2017. © 2016 Wiley Periodicals, Inc.

The changing landscape of phase II/III metastatic NSCLC clinical trials and the importance of biomarker selection criteria.

Over the last decade, new cytotoxic treatments and targeted therapies have altered treatment paradigms for patients with metastatic non-small cell lung cancer (NSCLC). We sought to analyze the impact of histology and biomarker selection criteria on outcomes of clinical trials in metastatic NSCLC reported over the last decade at the American Society of Clinical Oncology (ASCO) Annual Meeting. Data were collected from ASCO abstracts of Phase II-IV clinical trials for patients with metastatic NSCLC from 2004-2014. 770 of 2,989 identified metastatic NSCLC category abstracts met selection criteria. Despite a decline in the number of abstracts from 107 to 46 abstracts annually over this period, the proportion of trials with positive progression free survival (PFS) and overall survival (OS) outcomes has increased significantly. Trials with histology selection (6%) or molecular biomarker (15%) criteria were more likely to result in an improvement in PFS than those without selection criteria (21% vs. 8%, p = 0.0001 and 31% vs. 10%, p < 0.0001, respectively). These data demonstrate profound changes in the clinical trial landscape over the last 10 years with significantly increasing proportion of trials with positive outcomes. These changes are likely attributed to the use of histology and biomarker selection criteria in clinical trial design.

Bevacizumab in advanced NSCLC: chemotherapy partners and duration of use.

OPINION STATEMENT: Bevacizumab is an effective targeted therapy with demonstrated survival benefits for many patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Some patient populations are at higher risk for bleeding complications and bevacizumab should be avoided, but advanced age should not be used as the sole exclusion criterion for use. Bevacizumab is generally a well-tolerated therapy that can be safely given in combination with multiple chemotherapy agents in the induction and maintenance phases of therapy. The optimal maintenance strategy is yet to be determined and is the focus of ongoing trials, such as ECOG 5508. Early use of bevacizumab in the adjuvant setting and continued use in the second-line setting are being investigated in current clinical trials.

Prognostic Hematologic Biomarkers Following Immune Checkpoint Inhibition in Metastatic Uveal Melanoma.

Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9−7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6−8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5−5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1−4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0−3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00−1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00−1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.

Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma.

Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities. Results: Eighteen of the 20 patients (90%) required at least one treatment interruption due to adverse events (AEs), 11 patients (55%) required a dose reduction and 13 (65%) permanently discontinued therapy due to an AE. The nine patients who did not require dose reduction had been initiated on a lower starting dose of dabrafenib. The most common treatment-limiting AEs were recurrent pyrexia and chills (85%) and liver laboratory abnormalities (50%). The median total time on therapy was 148.5 days (range 19-383), 40.7% (range 5.2-100%) of the intended one-year duration. Conclusion: Adjuvant treatment of melanoma with combination D+T is associated with treatment-limiting toxicities in the majority of this patient group. Patients should be carefully monitored throughout therapy.

Prognostic and predictive value of neutrophil-to-lymphocyte ratio with adjuvant immunotherapy in stage III non-small-cell lung cancer.

BACKGROUND: Elevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit. METHODS: We identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS). RESULTS: The primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06-1.23; durvalumab: aHR 1.42, 95% CI 1.23-1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09-1.24; durvalumab: aHR 1.48, 95% CI 1.25-1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR. CONCLUSION: Pre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit.

Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor-Induced Myocarditis.

Background: Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis. Objectives: The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes. Methods: We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy. Results: Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis. Conclusions: ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis.

Teleoncology for Veterans: High Patient Satisfaction Coupled With Positive Financial and Environmental Impacts.

PURPOSE: There was rapid adoption of teleoncology care in the Veterans Health Administration during the COVID-19 pandemic. One third of 9 million Veterans Health Administration enrolled Veterans live in rural areas. Although digital solutions can expand capacity, enhance care access, and reduce financial burden, they may also exacerbate rural-urban health disparities. Careful evaluation of patients' perceptions and policy tradeoffs are necessary to optimize teleoncology postpandemic. METHODS: Patients with ≥ 1 teleoncology visit with medical, surgical, or radiation oncology between March 2020 and June 2020 were identified retrospectively. Validated, Likert-type survey assessing patient satisfaction was developed. Follow-up survey was conducted on patients with ≥ 1 teleoncology visit from August 2020 to January 2021. Travel distance, time, cost, and carbon dioxide emissions were calculated based on zip codes. RESULTS: A hundred surveys were completed (response rate, 62%). Patients overall were satisfied with teleoncology (83% Agree or Strongly Agree) but felt less satisfied than in-person visits (47% Agree or Strongly Agree). Audiovisual component improved patient perception of involvement in care, ability to self-manage health or medical needs, and comparability to in-person visits. Follow-up survey demonstrated similar satisfaction. Total travel-related savings are as follows: 86,470 miles, 84,374 minutes, $49,720 US dollars, and 35.5 metric tons of carbon dioxide. CONCLUSION: Veterans are broadly satisfied with teleoncology. Audiovisual capabilities are critical to satisfaction. This is challenging for rural populations with lack of technology access. Patients experienced financial and time savings, and society benefitted from reduced carbon emissions. Continued optimization is needed to enhance patient experience and address secondary effects.

Implementation of a Multidisciplinary Care Pathway via an Emergency Department-ICU to Improve Care of Emergency Department Patients Presenting With Leukostasis.

Leukostasis is a life-threatening complication of acute hyperleukocytic leukemia, and is associated with substantial mortality. Management of leukostasis requires time-sensitive diagnostics and therapeutics, and leukapheresis remains a mainstay of treatment in select patients. Leukapheresis requires coordination of multi-disciplinary resources, which can prove challenging in the emergency department setting, and delays in treatment due to the complexity and coordination required are common. The objective of this study was to assess the effect of utilization of an emergency department-ICU and a multidisciplinary care pathway on outcomes of critically ill leukostasis patients presenting to the emergency department. DESIGN: Retrospective cohort study. SETTING: Single large academic medical center in the United States. PATIENTS: Adult emergency department patients with signs and symptoms of leukostasis requiring emergent leukapheresis from 2012-2019. INTERVENTIONS: Implementation of a hybrid emergency department-ICU setting (emergency critical care center) and a multidisciplinary care pathway with members from Emergency Medicine, Hematology, Blood Bank, and Clinical Pathology. MEASUREMENTS AND MAIN RESULTS: A total of 70 patients were identified and included for analysis: 14 preemergency critical care center; 32 postemergency critical care center, premultidisciplinary care pathway; and 24 postemergency critical care center, postmultidisciplinary care pathway. A statistically significant reduction in the time from emergency department presentation to initiation of leukapheresis was observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (11.5 vs 7.9 vs 7.7 hr; p = 0.004). Statistically significant reductions in in-hospital mortality were observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (64.3% vs 21.9% vs 25.0%; p = 0.01). A trend toward decreased inpatient ICU utilization was observed, although was not statistically significant (35.7% vs 12.5% vs 25.0%; p = 0.14.). CONCLUSIONS AND RELEVANCE: Implementation of a multidisciplinary care pathway via use of an emergency department-ICU for critically ill patients with leukostasis was associated with statistically significant reductions in time to leukapheresis and in-hospital mortality. These findings suggest an emergency department-ICU model may allow for maximal resource and care coordination at the point of contact with critically ill patients and improved clinical outcomes.

Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data.

Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1-25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9-31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3-18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4-18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3-34.2) vs. 16.2 months (95% CI 7·9-24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports.

BACKGROUND: Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug's AEs (which may change during a drug's life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O'Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. METHODS: In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles' references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. RESULTS: One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing's syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. CONCLUSIONS: The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

Indoleamine 2,3-Dioxygenase (IDO) Inhibition as a Strategy to Augment Cancer Immunotherapy.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme of interest in immuno-oncology because of the immunosuppressive effects that result from its role in tryptophan catabolism. IDO is upregulated in malignancy and is associated with poor prognosis in multiple cancer types. IDO inhibitors have been developed to target IDO, both directly and indirectly. Pre-clinical data have shown combined IDO and checkpoint inhibition to be an efficacious strategy for tumor control. Clinical trials of IDO inhibitors with chemotherapy or immunotherapy are currently underway. This review describes the function of IDO and its inhibitors and summarizes the efficacy and toxicity data from recent clinical trials with these drugs.

Clinical Use of Anti-Xa Monitoring in Malignancy-Associated Thrombosis.

Introduction. Low molecular weight heparin (LMWH) is preferred for malignancy-associated venous thromboembolism (VTE). Many providers monitor LMWH with anti-Xa levels, despite little validation on correspondence with patient outcome. Methods. This is a retrospective, single institution study of anti-Xa measurement in malignancy-associated thrombosis. Cases were identified using the Electronic Data Warehouse, and inclusion was confirmed by two independent reviewers. Malignancy type, thrombotic history, measurement rationale and accuracy, clinical context, and management changes were evaluated. Results. 167 cases met inclusion criteria. There was no clear rationale for anti-Xa testing in 56%. Impaired renal function (10%), documented or suspected recurrent thrombosis despite anticoagulation (9%), and bleeding (6%) were the most common reasons for testing. Incorrect measurement occurred in 44%. Renal impairment was not a significant impetus for testing, as 70% had a GFR > 60. BMI > 30 was present in 40%, and 28% had a BMI < 25. Clinical impact was low, as only 11% of patients had management changes. Conclusions. Provider education in accuracy and rationale for anti-Xa testing is needed. Our study illustrates uncertainty of interpretation and clinical impact of routine anti-Xa testing, as management was affected in few patients. It is not yet clear in which clinical context providers should send anti-Xa levels.

Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma.

In the past 30 years, the incidence of esophageal adenocarcinoma (ACA) has increased significantly. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal ACA remains poor, with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because "alarm symptoms," such as dysphagia, occur at a late stage, and 2) high-grade dysplasia (HGD) and early ACA are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to ACA because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance, and treatment. Targeted agents against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF) are currently being evaluated for their role in combination chemotherapy for metastatic esophageal ACA. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell-surface receptors, and has the potential to evaluate an individual patient's gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for personalized treatment in the future.