Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We ...investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.
A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.
One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months).
Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.
Selecting the number of different classes that will be assumed to exist in the population is an important step in latent class analysis (LCA). The bootstrap likelihood ratio test (BLRT) provides a ...data-driven way to evaluate the relative adequacy of a (K - 1)-class model compared to a K-class model. However, very little is known about how to predict the power or the required sample size for the BLRT in LCA. Based on extensive Monte Carlo simulations, we provide practical effect size measures and power curves that can be used to predict power for the BLRT in LCA given a proposed sample size and a set of hypothesized population parameters. Estimated power curves and tables provide guidance for researchers wishing to size a study to have sufficient power to detect hypothesized underlying latent classes.
Despite recent methodological advances in latent class analysis (LCA) and a rapid increase in its application in behavioral research, complex research questions that include latent class variables ...often must be addressed by classifying individuals into latent classes and treating class membership as known in a subsequent analysis. Traditional approaches to classifying individuals based on posterior probabilities are known to produce attenuated estimates in the analytic model. We propose the use of a more inclusive LCA to generate posterior probabilities; this LCA includes additional variables present in the analytic model. A motivating empirical demonstration is presented, followed by a simulation study to assess the performance of the proposed strategy. Results show that with sufficient measurement quality or sample size, the proposed strategy reduces or eliminates bias.
Understanding temporal change in human behavior and psychological processes is a central issue in the behavioral sciences. With technological advances, intensive longitudinal data (ILD) are ...increasingly generated by studies of human behavior that repeatedly administer assessments over time. ILD offer unique opportunities to describe temporal behavioral changes in detail and identify related environmental and psychosocial antecedents and consequences. Traditional analytical approaches impose strong parametric assumptions about the nature of change in the relationship between time-varying covariates and outcomes of interest. This article introduces time-varying effect models (TVEMs) that explicitly model changes in the association between ILD covariates and ILD outcomes over time in a flexible manner. In this article, we describe unique research questions that the TVEM addresses, outline the model-estimation procedure, share a SAS macro for implementing the model, demonstrate model utility with a simulated example, and illustrate model applications in ILD collected as part of a smoking-cessation study to explore the relationship between smoking urges and self-efficacy during the course of the pre- and postcessation period.
To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.
Major inclusion ...criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m
once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events).
One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events.
Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.
The germination of soybean (
L.) seeds is critically affected by abiotic stresses which resulting in decreasing crop growth and yield. However; little is known about the physiological mechanisms of ...germination and the potential role of melatonin on soybean seed germination under drought, salt, cold, and heat stresses. Therefore, the current study investigated the possible effects of melatonin to enhance germination indices and other physiological attributes by alleviating the harmful impacts of these stresses during germination. Seeds of soybean were pre-treated (seed priming) with melatonin at MT1 (20 μmol L
), MT2 (50 μmol L
), MT3 (100 μmol L
), MT4 (200 μmol L
), and MT5 (300 μmol L
) and exposed to the four stresses (drought at PEG 15%, salt at 150mM, cold at 10 °C, and heat at 30 °C) . It was noted that MT1 (20 μmol L
), MT2 (50 μmol L
), and MT3 (100 μmol L
) remarkably improved the germination potential, germination rate, radical length, and biomass under given stresses. Furthermore, MT1, MT2, and MT3 progressively increased the proline to minimize the impact of drought, salt, cold, and heat stresses. In addition, all stresses significantly induced oxidative damage however, salt (150 mM NaCl) and heat (30 °C) stresses highly increased the malondialdehyde content (MDA) and hydrogen peroxide (H2O2) as compared to drought (PEG 15%) and cold (10 °C) stresses. Moreover, MT2 and MT3 significantly enhanced the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) to reduce the oxidative damage in soybean seeds during the germination. Overall, melatonin at 50 μmol L
and 100 μmol L
considerably mitigated the harmful impacts of drought, salt, cold, and heat stress by enhancing germination and other physiological mechanisms of soybean. This study could provide bases to enhance the melatonin-mediated tolerance of soybean and other related crops at early growth stages when exposed to abiotic stresses.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ...ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation.
The objective of this study was to evaluate the efficacy of abdominal cerclage via laparoscopy vs laparotomy and before vs after conception. We evaluated 16 studies of abdominal cerclage involving a ...total of 678 cases published between 1990 and 2013. We estimated the effect of laparotomy over laparoscopy and the effect of preconceptional over postconceptional cerclage using a generalized linear model by treating the success rates (third-trimester delivery and live birth) as dependent variables and laparotomy and preconceptional as independent factors. The results demonstrated that there was no difference in the rates of third-trimester delivery and live birth rates between preconceptional abdominal cerclage via laparoscopy (71.4%-83.3% and 90%-100%, respectively) or laparotomy (97.3%-100% and 100%, respectively). For postconceptional cerclage, the rates of third-trimester delivery and live birth via laparoscopy were 70% and 70% to 100%, respectively, and via laparotomy were 77.4% to 99.5% and 85.2% to 100%, respectively. There was no difference in the live birth rates when abdominal cerclage was performed before or during pregnancy. We concluded that the rates of third-trimester delivery and live birth after abdominal cerclage via laparoscopy are high and comparable to those via laparotomy. The efficacy of the procedure performed either before or during pregnancy is similar. Abdominal cerclage performed before conception is more practical than after conception. With the inherent advantages of laparoscopy over laparotomy, abdominal cerclage performed via laparoscopy is preferable, in particular when performed in non-pregnant women.
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