CA-125 early dynamics to predict overall survival in women with newly diagnosed advanced ovarian cancer based on meta-analysis data

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients’ monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov

Applicability of Preoperative Nuclear Morphometry to Evaluating Risk for Cervical Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Background: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma. Methods: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio), and nuclear area coefficient of variation (NACV). Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis. Results: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor) were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in nodenegative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site. Conclusion: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma

Factors associated with long-term use of hypnotics among patients with chronic insomnia.

This study investigated factors associated with long-term use of benzodiazepines (BZDs) or benzodiazepine receptor agonists (BzRAs) as hypnotics in patients with chronic insomnia. Consecutive patients (n = 140) with chronic insomnia were enrolled in this study (68 men and 72 women; mean age, 53.8 ± 10.8 years). All patients filled out a self-assessment questionnaire asking clinical descriptive variables at the baseline of the treatment period; patients received the usual dose of a single type of BZD or BzRA. The Pittsburgh Sleep Quality Index (PSQI) and the Zung Self-Rating Depression Scale were self-assessed at the baseline, and the former was re-evaluated at the time of cessation of medication or at the end of the 6-month treatment period. The PSQI included the following sub-items: evaluating sleep quality (C1), sleep latency (C2), sleep duration (C3), habitual sleep efficiency (C4), frequency of sleep disturbance (C5), use of sleeping medication (C6), and daytime dysfunction (C7). Among the patients, 54.6% needed to continue hypnotics for a 6-month treatment period. Logistic regression analysis revealed that, among descriptive variables, only the PSQI score appeared as a significant factor associated with long-term use {odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.0-4.0}. The receiver operating curve (ROC) analysis identified that the cut-off PSQI total score at the baseline for predicting long-term use was estimated at 13.5 points (area under the curve = 0.86, 95% CI = 0.8-0.92). Among the sub-items of PSQI, the increases in C1: (OR = 8.4, 95% CI = 2.4-30.0), C3: (OR = 3.6, 95% CI = 1.1-11.5), C4: (OR = 11.1, 95% CI = 3.6-33.9), and C6: (OR = 3.4, 95% CI = 1.9-6.2) scores were associated with long-term use. This study revealed that a high PSQI score at the baseline, particularly in the sub-items relating to sleep maintenance disturbance, is predictive of long-term hypnotic treatment. Our results imply the limitation of the effectiveness of hypnotic treatment alone for chronic insomnia

Logistic regression analysis of the associated factors for discontinuation of hypnotics using PSQI sub-item scores as explanatory variables.

<p>CI denotes confidence intervals.</p><p>ns =  not significant; PSQI =  Pittsburgh Sleep Quality Index.</p><p>Logistic regression analysis of the associated factors for discontinuation of hypnotics using PSQI sub-item scores as explanatory variables.</p

Comparison of demographic variables between the discontinued group and the long-term use group.

<p>Values are expressed as means ±SD. The Mann-Whitney U test was used for the comparison of continuous variables between the 2 groups as follows: age, duration of insomnia morbidity, dose of hypnotics, and SDS and PSQI scores. The chi-square test was used for the comparison of categorical variables between the 2 groups as follows: sex, marital status, educational background, occupation, and half-life of hypnotic.</p><p>ns =  not significant; SDS =  Zung Self-Rating Depression Scale; PSQI =  Pittsburgh Sleep Quality Index.</p><p>Comparison of demographic variables between the discontinued group and the long-term use group.</p

Predictive cut-off point of the Pittsburgh Sleep Quality Index for the long-term use of hypnotics estimated with the receiver operating characteristic (ROC) curve.

<p>CI denotes confidence intervals. AUC =  area under the curve.</p