Outcomes of pancreatic adenocarcinoma (PDA) remain dismal despite extensive clinical investigation. Combination chemotherapy provides modest improvements in survival above best supportive care, and ...immunotherapy has thus far not proven effective. Nevertheless, growing insight into antitumor immunity and the tumor microenvironment has inspired the discovery of novel agents targeting PDA. Oncolytic viruses represent an emerging class of immunotherapeutic agents that have undergone extensive preclinical investigation and warrant further investigation in well‐designed clinical trials.
In a trial comparing preoperative chemoradiotherapy and FOLFOX in patients with rectal cancer undergoing sphincter-sparing surgery, 5-year disease-free survival was 80.8% with FOLFOX and 78.6% with ...chemoradiotherapy.
Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent ...colorectal cancer and improve cancer-related outcomes.
Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored.
322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% confidence interval (CI), 42.4-80.6 and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (
= 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (
= 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity.
COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit.
This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.
Background
A blood assay measuring methylated BCAT1 and IKZF1 can detect recurrent colorectal cancer (CRC) with high sensitivity but suboptimal specificity. This study aimed to establish an upper ...reference limit (URL) of these biomarkers in a reference population without CRC, apply that threshold to detecting clinical recurrence in patients who had undergone definitive therapy for CRC, and compare the performance of the biomarkers with carcinoembryonic antigen (CEA).
Methods
The level of methylation was reported as the aggregate methylated BCAT1 and IKZF1 expressed as a percentage of total plasma DNA. A reference population of patients confirmed to have no colorectal neoplasia (n = 857) was used to determine the URL. Test accuracy for clinical recurrence was determined in a post‐treatment surveillance population (n = 549; 77 recurrence cases).
Results
A methylation level of 0.07%, corresponding to the 98th percentile in the reference population, was set as the URL. In the surveillance population, 60 patients had methylation levels above 0.07%, and 81.7% of these had recurrence. In comparison with no minimum threshold being applied, assay sensitivity with a URL of 0.07% yielded similar sensitivity (63.6% CI, 51.9%‐74.3% vs 64.9% CI, 53.8%‐74.7%; P = .87) and higher specificity (97.7% CI, 95.9%‐98.8% vs 91.3% CI, 88.4%‐93.5%; P < .001). The BCAT1/IKZF1 test was 2.5‐fold more sensitive than CEA for detecting recurrences considered amenable to surgery with curative intent (50.0% vs 20.8%; P = .016).
Conclusions
Applying a threshold for positivity to the methylated BCAT1/IKZF1 blood assay improved the specificity for CRC recurrence without compromising sensitivity. Both the sensitivity and the specificity were superior to those of CEA.
Applying a threshold for positivity to the methylated BCAT1/IKZF1 blood assay improves the specificity for colorectal cancer recurrence without compromising sensitivity. Higher specificity may reduce unnecessary follow‐up procedures and minimize patient anxiety.
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. The incidence of pancreatic cancer in African Americans is 50% to 90% higher than the incidence in other ...racial groups. African Americans also have the worst prognosis. This is an evidence-based review of pancreatic cancer in African Americans with particular emphasis on baseline characteristics, treatment, and survival.
We queried PubMed in search for articles describing racial disparities in pancreatic cancer. Two categories of terms were "anded" together: pancreatic cancer terms and race terms. The last search was performed on November 14, 2013.
We summarized the data on pancreatic cancer baseline characteristics, treatment, and survival for African Americans that we obtained from the following databases: (1) Surveillance, Epidemiology, and End Results, 1988-2008; (2) California Cancer Registry 1988-1998; (3) Cancer Survivor Program of Orange County/San Diego Imperial Organization for Cancer Control, 1988-1998; and (4) Harris County, 1998-2010.
Overall, pancreatic cancer survival of African Americans has not significantly improved over the past several decades despite advances in multimodality therapy; African Americans continue to face worse outcomes than whites. Although baseline characteristics, treatment, and biological factors offer some explanation, they do not completely explain the disparities in incidence and survival.
Physician Integrity, Templates, and the ‘F’ Word Musher, Daniel M.; Hayward, Christiana P.; Musher, Benjamin L.
The Journal of emergency medicine,
August 2019, 2019-Aug, 2019-08-00, 20190801, Letnik:
57, Številka:
2
Journal Article
Recenzirano
The medical profession is increasingly dependent upon electronic health records. Along with documented benefits, a number of potential ethical abuses have been outlined. Herein, we describe an ...ethical abuse that has received almost no attention, namely falsified medical records. We present three cases in which the medical record cited facts from history that were not elicited and findings from physical examination that was not performed. This is fraud. Prepopulated templates were almost certainly responsible. If a template is used, it must begin free of results–a skeleton onto which flesh is placed. If coders and third-party payers insist on having information than health care providers think relevant, then we, as a profession should “push back,” but a template that has been prepopulated puts fraudulent data into electronic health record, seriously damaging physician integrity.
The epidemiology of acute gastrointestinal illness is complex. The relevant infectious agents may spread from person to person or they may be acquired from a common food or environmental source, ...often water, but also from animal exposure. This article examines direct human-to-human spread of acute gastrointestinal illness, defined as a syndrome of vomiting, diarrhea, or both that begins abruptly in otherwise healthy persons and is most often self-limited.
This article examines direct human-to-human spread of acute gastrointestinal illness, defined as a syndrome of vomiting, diarrhea, or both that begins abruptly in otherwise healthy persons.
In our ever-shrinking world, widespread media coverage of infections, ranging from the severe acute respiratory syndrome (also known as SARS) and influenza in Asia to acute gastroenteritis on cruise ships and outbreaks in day-care centers in the United States, has raised public interest in contagious diseases to new heights. Our purpose in this article is to examine contagion (from the Latin,
tangere
, to touch) — direct human-to-human spread — of acute gastrointestinal illness, defined as a syndrome of vomiting, diarrhea, or both, that begins abruptly in otherwise healthy persons and is most often self-limited.
Unlike agents that cause contagious . . .
Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and ...4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma.
LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 μL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants.
Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 62% men and eight 38% women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4–10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 8% of 1237 events), lymphopenia (86 7% events), hyperglycaemia (70 6% events), leukopenia (63 5% events), hypertension (62 5% events), and hypoalbuminaemia (61 5% events). The most common adverse events attributed to LOAd703 were fever (14 67% of 21 patients), fatigue (eight 38%), chills (seven 33%), and elevated liver enzymes (alanine aminotransferase in five 24%, alkaline phosphatase in four 19%, and aspartate aminotransferase in four 19%), all of which were grade 1–2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25–66) of 18 patients evaluable for activity had an objective response.
Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing.
Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.
GOALS:To investigate trends in colorectal cancer (CRC) incidence and survival among Hispanics in Texas.
BACKGROUND:The incidence of CRC is rising among young adults in the United States. Given Texas’ ...large Hispanic population, investigating CRC trends in Texas may provide valuable insight into the future of CRC epidemiology in an ever-diversifying US population.
STUDY:Data from the Texas Cancer Registry (1995 to 2010) were used to calculate age-adjusted CRC rates based on the 2000 US standard population. Annual percentage change (APC) and 5-year cancer-specific survival (CSS) rates were reported by age, race/ethnicity, stage, and anatomic location.
RESULTS:Of 123,083 CRC cases, 11% occurred in individuals below 50 years old, 26% of whom were Hispanic. Incidence was highest among African Americans (AAs; 76.3/100,000), followed by non-Hispanic whites (NHWs; 60.2/100,000) and Hispanics (50.8/100,000). Although overall CRC incidence declined between 1995 and 2010 (APC, −1.8%; P<0.01), trends differed by age and race/ethnicity. Among individuals 50 years and above, the rate of decline was statistically significant among NHWs (APC, −2.4%; P<0.01) and AAs (APC, −1.3%; P<0.01) but not among Hispanics (APC, −0.6%; P=0.13). In persons aged 20 to 39 years, CRC incidence rose significantly among Hispanics (APC, 2.6%; P<0.01) and NHWs (APC, 2.4%; P<0.01), but not AAs (APC, 0.3%; P=0.75). CSS rates among Hispanics and NHWs were comparable across most age groups and cancer stages, whereas CSS rates among AAs were generally inferior to those observed among NHWs and Hispanics.
CONCLUSIONS:Although CRC incidence has declined in Texas, it is rising among young Hispanics and NHWs while declining more slowly among older Hispanics than among older NHWs and AAs.
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